Anthracycline-induced cardiotoxicity and renin-angiotensin-aldosterone system—from molecular mechanisms to therapeutic applications

Damiani RM, Moura DJ, Viau CM, Caceres RA, Henriques JAP, Saffi J (2016) Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone. Arch Toxicol 90(9):2063–2076. https://doi.org/10.1007/s00204-016-1759-y

Mitry MA, Edwards JG (2016) Doxorubicin induced heart failure: phenotype and molecular mechanisms. Int J Cardiol Heart Vasc 10:17–24. https://doi.org/10.1016/j.ijcha.2015.11.004

McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM (2017) Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther 31(1):63–75. https://doi.org/10.1007/s10557-016-6711-0

Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, Lopez Fernandez T, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM, Group ESD (2016) 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines:  The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 37(36):2768–2801. https://doi.org/10.1093/eurheartj/ehw211

Kremer LC, van Dalen EC, Offringa M, Ottenkamp J, Voute PA (2001) Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol 19(1):191–196. https://doi.org/10.1200/jco.2001.19.1.191

Renu K, Abilash VG, Tirupathi Pichiah PB, Arunachalam S (2018) Molecular mechanism of doxorubicin-induced cardiomyopathy - an update. Eur J Pharmacol 818:241–253. https://doi.org/10.1016/j.ejphar.2017.10.043

Buzdar AU, Marcus C, Smith TL, Blumenschein GR (1985) Early and delayed clinical cardiotoxicity of doxorubicin. Cancer 55(12):2761–2765

Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91(5):710–717

Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97(11):2869–2879. https://doi.org/10.1002/cncr.11407

Lipshultz SE, Lipsitz SR, Sallan SE, Dalton VM, Mone SM, Gelber RD, Colan SD (2005) Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 23(12):2629–2636. https://doi.org/10.1200/JCO.2005.12.121

Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP (1991) Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 324(12):808–815. https://doi.org/10.1056/nejm199103213241205

Singal PK, Iliskovic N (1998) Doxorubicin-induced cardiomyopathy. N Engl J Med 339(13):900–905. https://doi.org/10.1056/nejm199809243391307

van der Pal HJ, van Dalen EC, van Delden E, van Dijk IW, Kok WE, Geskus RB, Sieswerda E, Oldenburger F, Koning CC, van Leeuwen FE, Caron HN, Kremer LC (2012) High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol 30(13):1429–1437. https://doi.org/10.1200/jco.2010.33.4730

Armstrong GT, Joshi VM, Ness KK, Marwick TH, Zhang N, Srivastava D, Griffin BP, Grimm RA, Thomas J, Phelan D, Collier P, Krull KR, Mulrooney DA, Green DM, Hudson MM, Robison LL, Plana JC (2015) Comprehensive echocardiographic detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer: results from the St. Jude Lifetime Cohort Study. J Am Coll Cardiol 65(23):2511–2522. https://doi.org/10.1016/j.jacc.2015.04.013

Trouet A, Deprez-De Campeneere D (1979) Daunorubicin-DNA and doxorubicin-DNA. A review of experimental and clinical data. Cancer Chemother Pharmacol 2(1):77–79

Eom YW, Kim MA, Park SS, Goo MJ, Kwon HJ, Sohn S, Kim WH, Yoon G, Choi KS (2005) Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene 24(30):4765–4777. https://doi.org/10.1038/sj.onc.1208627

Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF (1984) Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science 226(4673):466–468

Capranico G, Tinelli S, Austin CA, Fisher ML, Zunino F (1992) Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta 1132(1):43–48

Simunek T, Sterba M, Popelova O, Adamcova M, Hrdina R, Gersl V (2009) Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 61(1):154–171

Gewirtz DA (1999) A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 57(7):727–741

Berthiaume JM, Wallace KB (2007) Adriamycin-induced oxidative mitochondrial cardiotoxicity. Cell Biol Toxicol 23(1):15–25. https://doi.org/10.1007/s10565-006-0140-y

Davies KJ, Doroshow JH (1986) Redox cycling of anthracyclines by cardiac mitochondria. I Anthracycline radical formation by NADH dehydrogenase. J Biol Chem 261(7):3060–3067

Ichikawa Y, Ghanefar M, Bayeva M, Wu R, Khechaduri A, Naga Prasad SV, Mutharasan RK, Naik TJ, Ardehali H (2014) Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest 124(2):617–630. https://doi.org/10.1172/jci72931

Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56(2):185–229. https://doi.org/10.1124/pr.56.2.6

Arola OJ, Saraste A, Pulkki K, Kallajoki M, Parvinen M, Voipio-Pulkki LM (2000) Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res 60(7):1789–1792

Zhang YW, Shi J, Li YJ, Wei L (2009) Cardiomyocyte death in doxorubicin-induced cardiotoxicity. Arch Immunol Ther Exp (Warsz) 57(6):435–445. https://doi.org/10.1007/s00005-009-0051-8

Maejima Y, Adachi S, Ito H, Hirao K, Isobe M (2008) Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage. Aging Cell 7(2):125–136. https://doi.org/10.1111/j.1474-9726.2007.00358.x

De Angelis A, Piegari E, Cappetta D, Marino L, Filippelli A, Berrino L, Ferreira-Martins J, Zheng H, Hosoda T, Rota M, Urbanek K, Kajstura J, Leri A, Rossi F, Anversa P (2010) Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation 121(2):276–292. https://doi.org/10.1161/circulationaha.109.895771

Martin E, Thougaard AV, Grauslund M, Jensen PB, Bjorkling F, Hasinoff BB, Tjornelund J, Sehested M, Jensen LH (2009) Evaluation of the topoisomerase II-inactive bisdioxopiperazine ICRF-161 as a protectant against doxorubicin-induced cardiomyopathy. Toxicology 255(1–2):72–79. https://doi.org/10.1016/j.tox.2008.10.011

Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, Yeh ET (2012) Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 18(11):1639–1642. https://doi.org/10.1038/nm.2919

George AJ, Thomas WG, Hannan RD (2010) The renin–angiotensin system and cancer: old dog, new tricks. Nat Rev Cancer 10(11):745–759. https://doi.org/10.1038/nrc2945

Singh KD, Karnik SS (2016) Angiotensin receptors: structure, function, signaling and clinical applications. J Cell Signal 1(2). https://doi.org/10.4172/jcs.1000111

Iwai N, Inagami T (1992) Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Lett 298(2–3):257–260. https://doi.org/10.1016/0014-5793(92)80071-n

Uehara Y, S-i M, Yahiro E, Saku K (2013) Non-ACE pathway-induced angiotensin II production. Curr Pharm Des 19(17):3054–3059

Urata H, Nishimura H, Ganten D (1996) Chymase-dependent angiotensin II forming systems in humans. Am J Hypertens 9(3):277–284. https://doi.org/10.1016/0895-7061(95)00349-5

Li Q, Feenstra M, Pfaffendorf M, Eijsman L, van Zwieten PA (1997) Comparative vasoconstrictor effects of angiotensin II, III, and IV in human isolated saphenous vein. J Cardiovasc Pharmacol 29(4):451–456. https://doi.org/10.1097/00005344-199,704,000-00004

Aguilera G (1992) Role of angiotensin II receptor subtypes on the regulation of aldosterone secretion in the adrenal glomerulosa zone in the rat. Mol Cell Endocrinol 90(1):53–60. https://doi.org/10.1016/0303-7207(92)90101-b

Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz J, Riede UN, Drexler H (1994) Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation 89(5):2273–2282. https://doi.org/10.1161/01.cir.89.5.2273

Wolf G, Wenzel U, Burns KD, Harris RC, Stahl RA, Thaiss F (2002) Angiotensin II activates nuclear transcription factor-kappaB through AT1 and AT2 receptors. Kidney Int 61(6):1986–1995. https://doi.org/10.1046/j.1523-1755.2002.00365.x

Sadoshima J, Izumo S (1993) Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 73(3):413–423. https://doi.org/10.1161/01.res.73.3.413

Yamada K, Iyer SN, Chappell MC, Ganten D, Ferrario CM (1998) Converting enzyme determines plasma clearance of angiotensin-(1–7). Hypertension 32(3):496–502. https://doi.org/10.1161/01.hyp.32.3.496

AbdAlla S, Lother H, Abdel-tawab AM, Quitterer U (2001) The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem 276(43):39721–39,726. https://doi.org/10.1074/jbc.M105253200

Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, Albiston AL (2004) The angiotensin IV/AT4 receptor. Cell Mol Life Sci 61(21):2728–2737. https://doi.org/10.1007/s00018-004-4246-1

Kramar EA, Harding JW, Wright JW (1997) Angiotensin II- and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes. Regul Pept 68(2):131–138. https://doi.org/10.1016/s0167-0115(96)02116-7

Handa RK, Krebs LT, Harding JW, Handa SE (1998) Angiotensin IV AT4-receptor system in the rat kidney. Am J Physiol 274(2):F290–F299. https://doi.org/10.1152/ajprenal.1998.274.2.F290

Park BM, Cha SA, Lee SH, Kim SH (2016) Angiotensin IV protects cardiac reperfusion injury by inhibiting apoptosis and inflammation via AT4R in rats. Peptides 79:66–74. https://doi.org/10.1016/j.peptides.2016.03.017

Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S (2000) A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res 87(5):E1–E9. https://doi.org/10.1161/01.res.87.5.e1

Liu Y, Li B, Wang X, Li G, Shang R, Yang J, Wang J, Zhang M, Chen Y, Zhang Y, Zhang C, Hao P (2015) Angiotensin-(1–7) suppresses hepatocellular carcinoma growth and angiogenesis via complex interactions of angiotensin II type 1 receptor, angiotensin II type 2 receptor and Mas receptor. Mol Med 21:626–636. https://doi.org/10.2119/molmed.2015.00022

Karnik SS, Singh KD, Tirupula K, Unal H (2017) Significance of angiotensin 1–7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR Review 22. Br J Pharmacol 174(9):737–753. https://doi.org/10.1111/bph.13742

Fontes MA, Silva LC, Campagnole-Santos MJ, Khosla MC, Guertzenstein PG, Santos RA (1994) Evidence that angiotensin-(1–7) plays a role in the central control of blood pressure at the ventro-lateral medulla acting through specific receptors. Brain Res 665(1):175–180. https://doi.org/10.1016/0006-8993(94)91171-1

Li P, Chappell MC, Ferrario CM, Brosnihan KB (1997) Angiotensin-(1–7) augments bradykinin-induced vasodilation by competing with ACE and releasing nitric oxide. Hypertension 29(1 Pt 2):394–400. https://doi.org/10.1161/01.hyp.29.1.394

McKinney CA, Fattah C, Loughrey CM, Milligan G, Nicklin SA (2014) Angiotensin-(1–7) and angiotensin-(1–9): function in cardiac and vascular remodelling. Clin Sci (Lond) 126(12):815–827. https://doi.org/10.1042/cs20130436

Gonzalez L, Novoa U, Moya J, Gabrielli L, Jalil JE, Garcia L, Chiong M, Lavandero S, Ocaranza MP (2018) Angiotensin-(1–9) reduces cardiovascular and renal inflammation in experimental renin-independent hypertension. Biochem Pharmacol 156:357–370. https://doi.org/10.1016/j.bcp.2018.08.045

Ocaranza MP, Moya J, Barrientos V, Alzamora R, Hevia D, Morales C, Pinto M, Escudero N, Garcia L, Novoa U, Ayala P, Diaz-Araya G, Godoy I, Chiong M, Lavandero S, Jalil JE, Michea L (2014) Angiotensin-(1–9) reverses experimental hypertension and cardiovascular damage by inhibition of the angiotensin converting enzyme/Ang II axis. J Hypertens 32(4):771–783. https://doi.org/10.1097/hjh.0000000000000094

Ocaranza MP, Lavandero S, Jalil JE, Moya J, Pinto M, Novoa U, Apablaza F, Gonzalez L, Hernandez C, Varas M, Lopez R, Godoy I, Verdejo H, Chiong M (2010) Angiotensin-(1–9) regulates cardiac hypertrophy in vivo and in vitro. J Hypertens 28(5):1054–1064. https://doi.org/10.1097/hjh.0b013e328335d291

Kakiki M, Morohashi K, Nomura M, Omura T, Horie T (1997) Expression of aldosterone synthase cytochrome P450 (P450aldo) mRNA in rat adrenal glomerulosa cells by angiotensin II type 1 receptor. Endocr Res 23(4):277–295

Cannavo A, Bencivenga L, Liccardo D, Elia A, Marzano F, Gambino G, D’Amico ML, Perna C, Ferrara N, Rengo G, Paolocci N (2018) Aldosterone and mineralocorticoid receptor system in cardiovascular physiology and pathophysiology. Oxidative Med Cell Longev 2018:1204598. https://doi.org/10.1155/2018/1204598

Paul M, Poyan Mehr A, Kreutz R (2006) Physiology of local renin-angiotensin systems. Physiol Rev 86(3):747–803. https://doi.org/10.1152/physrev.00036.2005

Zhuo JL, Li XC (2011) New insights and perspectives on intrarenal renin-angiotensin system: focus on intracrine/intracellular angiotensin II. Peptides 32(7):1551–1565. https://doi.org/10.1016/j.peptides.2011.05.012

Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 36(10):1953–2041. https://doi.org/10.1097/hjh.0000000000001940

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C (2017) 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 70(6):776–803. https://doi.org/10.1016/j.jacc.2017.04.025

Ibrahim SL, Jiroutek MR, Holland MA, Sutton BS (2016) Utilization of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in patients diagnosed with diabetes: Analysis from the National Ambulatory Medical Care Survey. Prev Med Rep 3:166–170. https://doi.org/10.1016/j.pmedr.2016.01.005

Kohara K, Brosnihan KB, Ferrario CM (1993) Angiotensin(1–7) in the spontaneously hypertensive rat. Peptides 14(5):883–891. https://doi.org/10.1016/0196-9781(93)90063-m

Vekris A, Godard F, Haaz M-C, Robert J, Bonnet J (2001) Doxorubicin-induced alterations of the gene expression profiles of leukemia cells in culture using cDNA microarrays. Nat Genet 27(S4):44–44. https://doi.org/10.1038/87014

Boucek RJ Jr, Miracle A, Anderson M, Engelman R, Atkinson J, Dodd DA (1999) Persistent effects of doxorubicin on cardiac gene expression. J Mol Cell Cardiol 31(8):1435–1446. https://doi.org/10.1006/jmcc.1999.0972

Zheng M, Kang YM, Liu W, Zang WJ, Bao CY, Qin DN (2012) Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure. PLoS One 7(11):e48771. https://doi.org/10.1371/journal.pone.0048771

Arozal W, Watanabe K, Veeraveedu PT, Thandavarayan RA, Harima M, Sukumaran V, Suzuki K, Tachikawa H, Kodama M, Aizawa Y (2010) Beneficial effects of angiotensin II receptor blocker, olmesartan, in limiting the cardiotoxic effect of daunorubicin in rats. Free Radic Res 44(11):1369–1377. https://doi.org/10.3109/10715762.2010.509399

Rashikh A, Pillai KK, Najmi AK (2014) Protective effect of a direct renin inhibitor in acute murine model of cardiotoxicity and nephrotoxicity. Fundam Clin Pharmacol 28(5):489–500. https://doi.org/10.1111/fcp.12054

Okumura K, Jin D, Takai S, Miyazaki M (2002) Beneficial effects of angiotensin-converting enzyme inhibition in adriamycin-induced cardiomyopathy in hamsters. Jpn J Pharmacol 88(2):183–188

Zhang J, Herman EH, Ferrans VJ (1994) Effects of ICRF-186 [(l)1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] on the toxicity of doxorubicin in spontaneously hypertensive rats. Toxicology 92(1–3):179–192. https://doi.org/10.1016/0300-483x(94)90176-7

Rook M, Lely AT, Kramer AB, van Goor H, Navis G (2005) Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage. Nephrol Dial Transplant 20(1):59–64. https://doi.org/10.1093/ndt/gfh579

Huang CY, Chen JY, Kuo CH, Pai PY, Ho TJ, Chen TS, Tsai FJ, Padma VV, Kuo WW, Huang CY (2018) Mitochondrial ROS-induced ERK1/2 activation and HSF2-mediated AT1 R upregulation are required for doxorubicin-induced cardiotoxicity. J Cell Physiol 233(1):463–475. https://doi.org/10.1002/jcp.25905

Zong WN, Yang XH, Chen XM, Huang HJ, Zheng HJ, Qin XY, Yong YH, Cao K, Huang J, Lu XZ (2011) Regulation of angiotensin-(1–7) and angiotensin II type 1 receptor by telmisartan and losartan in adriamycin-induced rat heart failure. Acta Pharmacol Sin 32(11):1345–1350. https://doi.org/10.1038/aps.2011.96

Tateishi Y, Ariyoshi M, Igarashi R, Hara H, Mizuguchi K, Seto A, Nakai A, Kokubo T, Tochio H, Shirakawa M (2009) Molecular basis for SUMOylation-dependent regulation of DNA binding activity of heat shock factor 2. J Biol Chem 284(4):2435–2447. https://doi.org/10.1074/jbc.M806392200

Toko H, Oka T, Zou Y, Sakamoto M, Mizukami M, Sano M, Yamamoto R, Sugaya T, Komuro I (2002) Angiotensin II type 1a receptor mediates doxorubicin-induced cardiomyopathy. Hypertens Res 25(4):597–603

Sharov VG, Todor A, Suzuki G, Morita H, Tanhehco EJ, Sabbah HN (2003) Hypoxia, angiotensin II, and norepinephrine mediated apoptosis is stimulus specific in canine failed cardiomyocytes: a role for p38 MAPK, Fas-L and cyclin D1. Eur J Heart Fail 5(2):121–129. https://doi.org/10.1016/s1388-9842(02)00254-4

Wang L-P, Fan S-J, Li S-M, Wang X-J, Gao J-L, Yang X-H (2016) Protective role of ACE2-Ang-(1–7)-Mas in myocardial fibrosis by downregulating KCa3.1 channel via ERK1/2 pathway. Pflugers Arch - Eur J Physiol 468(11):2041–2051. https://doi.org/10.1007/s00424-016-1875-9

Kawano H, Do YS, Kawano Y, Starnes V, Barr M, Law RE, Hsueh WA (2000) Angiotensin II has multiple profibrotic effects in human cardiac fibroblasts. Circulation 101(10):1130–1137. https://doi.org/10.1161/01.cir.101.10.1130

Xu J, Carretero OA, Liao TD, Peng H, Shesely EG, Xu J, Liu TS, Yang JJ, Reudelhuber TL, Yang XP (2010) Local angiotensin II aggravates cardiac remodeling in hypertension. Am J Physiol Heart Circ Physiol 299(5):H1328–H1338. https://doi.org/10.1152/ajpheart.00538.2010

Taskin E, Kindap EK, Ozdogan K, Aycan MB, Dursun N (2016) Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II. Cytotechnology 68(1):33–43. https://doi.org/10.1007/s10616-014-9748-6

Arozal W, Watanabe K, Veeraveedu PT, Thandavarayan RA, Harima M, Sukumaran V, Suzuki K, Kodama M, Aizawa Y (2010) Effect of telmisartan in limiting the cardiotoxic effect of daunorubicin in rats. J Pharm Pharmacol 62(12):1776–1783. https://doi.org/10.1111/j.2042-7158.2010.01196.x

Francis J, Wei SG, Weiss RM, Felder RB (2004) Brain angiotensin-converting enzyme activity and autonomic regulation in heart failure. Am J Physiol Heart Circ Physiol 287(5):H2138–H2146. https://doi.org/10.1152/ajpheart.00112.2004

McKinley MJ, McAllen RM, Pennington GL, Smardencas A, Weisinger RS, Oldfield BJ (1996) Physiological actions of angiotensin II mediated by AT1 AND AT2 receptors in the brain. Clin Exp Pharmacol Physiol 23(Suppl 3):S99–S104. https://doi.org/10.1111/j.1440-1681.1996.tb02821.x

Oldfield BJ, Davern PJ, Giles ME, Allen AM, Badoer E, McKinley MJ (2001) Efferent neural projections of angiotensin receptor (AT1) expressing neurones in the hypothalamic paraventricular nucleus of the rat. J Neuroendocrinol 13(2):139–146

Kang YM, Zhang ZH, Xue B, Weiss RM, Felder RB (2008) Inhibition of brain proinflammatory cytokine synthesis reduces hypothalamic excitation in rats with ischemia-induced heart failure. Am J Physiol Heart Circ Physiol 295(1):H227–H236. https://doi.org/10.1152/ajpheart.01157.2007

Jones LW, Haykowsky M, Peddle CJ, Joy AA, Pituskin EN, Tkachuk LM, Courneya KS, Slamon DJ, Mackey JR (2007) Cardiovascular risk profile of patients with HER2/neu-positive breast cancer treated with anthracycline-taxane-containing adjuvant chemotherapy and/or trastuzumab. Cancer Epidemiol Biomark Prev 16(5):1026–1031. https://doi.org/10.1158/1055-9965.EPI-06-0870

Rabinovich I, Sebastiao APM, Lima RS, Urban CA, Junior ES, Anselmi KF, Elifio-Esposito S, De Noronha L, Moreno-Amaral AN (2018) Cancer stem cell markers ALDH1 and CD44+/CD24- phenotype and their prognosis impact in invasive ductal carcinoma. Eur J Histochem 62(3). https://doi.org/10.4081/ejh.2018.2943

Silveira KD, Barroso LC, Vieira AT, Cisalpino D, Lima CX, Bader M, Arantes RM, Dos Santos RA, Simoes ESAC, Teixeira MM (2013) Beneficial effects of the activation of the angiotensin-(1–7) MAS receptor in a murine model of adriamycin-induced nephropathy. PLoS One 8(6):e66082. https://doi.org/10.1371/journal.pone.0066082

Hullin R, Metrich M, Sarre A, Basquin D, Maillard M, Regamey J, Martin D (2018) Diverging effects of enalapril or eplerenone in primary prevention against doxorubicin-induced cardiotoxicity. Cardiovasc Res 114(2):272–281. https://doi.org/10.1093/cvr/cvx162

Lother A, Bergemann S, Kowalski J, Huck M, Gilsbach R, Bode C, Hein L (2018) Inhibition of the cardiac myocyte mineralocorticoid receptor ameliorates doxorubicin-induced cardiotoxicity. Cardiovasc Res 114(2):282–290. https://doi.org/10.1093/cvr/cvx078

Meinel S, Gekle M, Grossmann C (2014) Mineralocorticoid receptor signaling: crosstalk with membrane receptors and other modulators. Steroids 91:3–10. https://doi.org/10.1016/j.steroids.2014.05.017

Liu G, Liu Y, Wang R, Hou T, Chen C, Zheng S, Dong Z (2016) Spironolactone Attenuates Doxorubicin-induced Cardiotoxicity in Rats. Cardiovasc Ther 34(4):216–224. https://doi.org/10.1111/1755-5922.12189

Node K, Kitakaze M, Kosaka H, Minamino T, Mori H, Hori M (1998) Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition against ischemic myocardial injury. Hypertension 31(6):1290–1298

Ferrari R, Cargnoni A, Curello S, Ceconi C, Boraso A, Visioli O (1992) Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: insight into its mechanism of action. J Cardiovasc Pharmacol 20(5):694–704

Li K, Chen X (1987) Protective effects of captopril and enalapril on myocardial ischemia and reperfusion damage of rat. J Mol Cell Cardiol 19(9):909–915

Zhang YC, Tang Y, Zhang M, Chen J, Zhou Q, Sun YG, Chen MT, Xu WP (2012) Fosinopril attenuates the doxorubicin-induced cardiomyopathy by restoring the function of sarcoplasmic reticulum. Cell Biochem Biophys 64(3):205–211. https://doi.org/10.1007/s12013-012-9386-6

Vaynblat M, Shah HR, Bhaskaran D, Ramdev G, Davis WJ 3rd, Cunningham JN Jr, Chiavarelli M (2002) Simultaneous angiotensin converting enzyme inhibition moderates ventricular dysfunction caused by doxorubicin. Eur J Heart Fail 4(5):583–586

Hiona A, Lee AS, Nagendran J, Xie X, Connolly AJ, Robbins RC, Wu JC (2011) Pretreatment with angiotensin-converting enzyme inhibitor improves doxorubicin-induced cardiomyopathy via preservation of mitochondrial function. J Thorac Cardiovasc Surg 142(2):396–403.e393. https://doi.org/10.1016/j.jtcvs.2010.07.097

Cernecka H, Ochodnicka-Mackovicova K, Kucerova D, Kmecova J, Nemcekova V, Doka G, Kyselovic J, Krenek P, Ochodnicky P, Klimas J (2013) Enalaprilat increases PPARbeta/delta expression, without influence on PPARalpha and PPARgamma, and modulate cardiac function in sub-acute model of daunorubicin-induced cardiomyopathy. Eur J Pharmacol 714(1–3):472–477. https://doi.org/10.1016/j.ejphar.2013.06.040

Abd El-Aziz MA, Othman AI, Amer M, El-Missiry MA (2001) Potential protective role of angiotensin-converting enzyme inhibitors captopril and enalapril against adriamycin-induced acute cardiac and hepatic toxicity in rats. J Appl Toxicol 21(6):469–473. https://doi.org/10.1002/jat.782

Scribner AW, Loscalzo J, Napoli C (2003) The effect of angiotensin-converting enzyme inhibition on endothelial function and oxidant stress. Eur J Pharmacol 482(1–3):95–99. https://doi.org/10.1016/j.ejphar.2003.10.002

Richard C, Lauzier B, Delemasure S, Talbot S, Ghibu S, Collin B, Senecal J, Menetrier F, Vergely C, Couture R, Rochette L (2008) Effects of angiotensin-1 converting enzyme inhibition on oxidative stress and bradykinin receptor expression during doxorubicin-induced cardiomyopathy in rats. J Cardiovasc Pharmacol 52(3):278–285. https://doi.org/10.1097/FJC.0b013e3181865f28

Subissi A, Evangelista S, Giachetti A (1999) Preclinical profile of zofenopril: an angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovasc Drug Rev 17(2):115–133. https://doi.org/10.1111/j.1527-3466.1999.tb00008.x

Mak IT, Freedman AM, Dickens BF, Weglicki WB (1990) Protective effects of sulfhydryl-containing angiotensin converting enzyme inhibitors against free radical injury in endothelial cells. Biochem Pharmacol 40(9):2169–2175

Sacco G, Mario B, Lopez G, Evangelista S, Manzini S, Maggi CA (2009) ACE inhibition and protection from doxorubicin-induced cardiotoxicity in the rat. Vasc Pharmacol 50(5–6):166–170. https://doi.org/10.1016/j.vph.2009.01.001

Sacco G, Bigioni M, Evangelista S, Goso C, Manzini S, Maggi CA (2001) Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat. Eur J Pharmacol 414(1):71–78

Bozcali E, Dedeoglu DB, Karpuz V, Suzer O, Karpuz H (2012) Cardioprotective effects of zofenopril, enalapril and valsartan against ischaemia/reperfusion injury as well as doxorubicin cardiotoxicity. Acta Cardiol 67(1):87–96. https://doi.org/10.2143/ac.67.1.2146570

Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Módis K, Panopoulos P, Asimakopoulou A, Gerö D, Sharina I, Martin E, Szabo C (2012) Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci 109(23):9161–9166. https://doi.org/10.1073/pnas.1202916109

Zanardo RCO, Brancaleone V, Distrutti E, Fiorucci S, Cirino G, Wallace JL (2006) Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation. FASEB J 20(12):2118–2120. https://doi.org/10.1096/fj.06-6270fje

Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L, Jiao X, Scalia R, Kiss L, Szabo C, Kimura H, Chow C-W, Lefer DJ (2007) Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci 104(39):15560–15,565. https://doi.org/10.1073/pnas.0705891104

Monti M, Terzuoli E, Ziche M, Morbidelli L (2013) The sulphydryl containing ACE inhibitor Zofenoprilat protects coronary endothelium from Doxorubicin-induced apoptosis. Pharmacol Res 76:171–181. https://doi.org/10.1016/j.phrs.2013.08.003

Maeda A, Honda M, Kuramochi T, Tanaka K, Takabatake T (1997) An angiotensin-converting enzyme inhibitor protects against doxorubicin-induced impairment of calcium handling in neonatal rat cardiac myocytes. Clin Exp Pharmacol Physiol 24(9–10):720–726

Bauer IH, Reams GP, Wu Z, Lau-Sieckman A (1995) Effects of losartan on the renin-angiotensin-aldosterone axis in essential hypertension. J Hum Hypertens 9(4):237–243

Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, Ferrario CM (2004) Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension 43(5):970–976. https://doi.org/10.1161/01.HYP.0000124667.34652.1a

Soga M, Kamal FA, Watanabe K, Ma M, Palaniyandi S, Prakash P, Veeraveedu P, Mito S, Kunisaki M, Tachikawa H, Kodama M, Aizawa Y (2006) Effects of angiotensin II receptor blocker (candesartan) in daunorubicin-induced cardiomyopathic rats. Int J Cardiol 110(3):378–385. https://doi.org/10.1016/j.ijcard.2005.08.061

Iqbal M, Dubey K, Anwer T, Ashish A, Pillai KK (2008) Protective effects of telmisartan against acute doxorubicin-induced cardiotoxicity in rats. Pharmacol Rep 60(3):382–390

Ibrahim MA, Ashour OM, Ibrahim YF, El-Bitar HI, Gomaa W, Abdel-Rahim SR (2009) Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity. Pharmacol Res 60(5):373–381. https://doi.org/10.1016/j.phrs.2009.05.007

Shao J, Nangaku M, Inagi R, Kato H, Miyata T, Matsusaka T, Noiri E, Fujita T (2007) Receptor-independent intracellular radical scavenging activity of an angiotensin II receptor blocker. J Hypertens 25(8):1643–1649. https://doi.org/10.1097/HJH.0b013e328165d159

Yamagishi S, Takeuchi M (2005) Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property. Med Hypotheses 64(3):476–478. https://doi.org/10.1016/j.mehy.2004.09.015

Fogli S, Nieri P, Breschi MC (2004) The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J 18(6):664–675. https://doi.org/10.1096/fj.03-0724rev

Kalivendi SV, Kotamraju S, Zhao H, Joseph J, Kalyanaraman B (2001) Doxorubicin-induced apoptosis is associated with increased transcription of endothelial nitric-oxide synthase. Effect of antiapoptotic antioxidants and calcium. J Biol Chem 276(50):47266–47,276. https://doi.org/10.1074/jbc.M106829200

Hahn AW, Jonas U, Buhler FR, Resink TJ (1994) Activation of human peripheral monocytes by angiotensin II. FEBS Lett 347(2–3):178–180. https://doi.org/10.1016/0014-5793(94)00531-1

Matouk AI, Taye A, Heeba GH, El-Moselhy MA (2013) Quercetin augments the protective effect of losartan against chronic doxorubicin cardiotoxicity in rats. Environ Toxicol Pharmacol 36(2):443–450. https://doi.org/10.1016/j.etap.2013.05.006

Loizzo MR, Said A, Tundis R, Rashed K, Statti GA, Hufner A, Menichini F (2007) Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phytother Res 21(1):32–36. https://doi.org/10.1002/ptr.2008

Sakr HF, Abbas AM, Elsamanoudy AZ (2016) Effect of valsartan on cardiac senescence and apoptosis in a rat model of cardiotoxicity. Can J Physiol Pharmacol 94(6):588–598. https://doi.org/10.1139/cjpp-2015-0461

Aupperle H, Garbade J, Schubert A, Barten M, Dhein S, Schoon HA, Mohr FW (2007) Effects of autologous stem cells on immunohistochemical patterns and gene expression of metalloproteinases and their tissue inhibitors in doxorubicin cardiomyopathy in a rabbit model. Vet Pathol 44(4):494–503. https://doi.org/10.1354/vp.44-4-494

Kizaki K, Ito R, Okada M, Yoshioka K, Uchide T, Temma K, Mutoh K, Uechi M, Hara Y (2006) Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice. Pharmacol Res 53(4):341–346. https://doi.org/10.1016/j.phrs.2006.01.001

Rutschow S, Li J, Schultheiss HP, Pauschinger M (2006) Myocardial proteases and matrix remodeling in inflammatory heart disease. Cardiovasc Res 69(3):646–656. https://doi.org/10.1016/j.cardiores.2005.12.009

Chow AK, Cena J, Schulz R (2007) Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature. Br J Pharmacol 152(2):189–205. https://doi.org/10.1038/sj.bjp.0707344

Chang SA, Lim BK, Lee YJ, Hong MK, Choi JO, Jeon ES (2015) A Novel angiotensin type I receptor antagonist, fimasartan, prevents doxorubicin-induced cardiotoxicity in rats. J Korean Med Sci 30(5):559–568. https://doi.org/10.3346/jkms.2015.30.5.559

Ezekowitz JA, McAlister FA (2009) Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials. Eur Heart J 30(4):469–477. https://doi.org/10.1093/eurheartj/ehn543

Rashikh A, Ahmad SJ, Pillai KK, Kohli K, Najmi AK (2012) Aliskiren attenuates myocardial apoptosis and oxidative stress in chronic murine model of cardiomyopathy. Biomed Pharmacother 66(2):138–143. https://doi.org/10.1016/j.biopha.2011.11.020

Akolkar G, Bhullar N, Bews H, Shaikh B, Premecz S, Bordun KA, Cheung DY, Goyal V, Sharma AK, Garber P, Singal PK, Jassal DS (2015) The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity. Cardiovasc Ultrasound 13:18. https://doi.org/10.1186/s12947-015-0011-x

Schneider M, Ackermann K, Stuart M, Wex C, Protzer U, Schatzl HM, Gilch S (2012) Severe acute respiratory syndrome coronavirus replication is severely impaired by MG132 due to proteasome-independent inhibition of M-calpain. J Virol 86(18):10112–10122. https://doi.org/10.1128/JVI.01001-12

Lu L, Wu W, Yan J, Li X, Yu H, Yu X (2009) Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure. Int J Cardiol 134(1):82–90. https://doi.org/10.1016/j.ijcard.2008.01.043

Lai L, Chen J, Wang N, Zhu G, Duan X, Ling F (2017) MiRNA-30e mediated cardioprotection of ACE2 in rats with Doxorubicin-induced heart failure through inhibiting cardiomyocytes autophagy. Life Sci 169:69–75. https://doi.org/10.1016/j.lfs.2016.09.006

Ma H, Kong J, Wang YL, Li JL, Hei NH, Cao XR, Yang JJ, Yan WJ, Liang WJ, Dai HY, Dong B (2017) Angiotensin-converting enzyme 2 overexpression protects against doxorubicin-induced cardiomyopathy by multiple mechanisms in rats. Oncotarget 8(15):24548–24563. https://doi.org/10.18632/oncotarget.15595

Zou MH, Xie Z (2013) Regulation of interplay between autophagy and apoptosis in the diabetic heart: new role of AMPK. Autophagy 9(4):624–625. https://doi.org/10.4161/auto.23577

Singla DK, Ahmed A, Singla R, Yan B (2012) Embryonic stem cells improve cardiac function in Doxorubicin-induced cardiomyopathy mediated through multiple mechanisms. Cell Transplant 21(9):1919–1930. https://doi.org/10.3727/096368911X627552

Ren D, Zhu Q, Li J, Ha T, Wang X, Li Y (2012) Overexpression of angiopoietin-1 reduces doxorubicin-induced apoptosis in cardiomyocytes. J Biomed Res 26(6):432–438. https://doi.org/10.7555/JBR.26.20120006

Liu HZ, Gao CY, Wang XQ, Fu HX, Yang HH, Wang XP, Liu YH, Li MW, Niu ZM, Dai GY, Qi DT, Zhang Y (2012) Angiotensin(1–7) attenuates left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy. Zhonghua Xin Xue Guan Bing Za Zhi 40(3):219–224

Zhong J, Guo D, Chen CB, Wang W, Schuster M, Loibner H, Penninger JM, Scholey JW, Kassiri Z, Oudit GY (2011) Prevention of angiotensin II-mediated renal oxidative stress, inflammation, and fibrosis by angiotensin-converting enzyme 2. Hypertension 57(2):314–322. https://doi.org/10.1161/HYPERTENSIONAHA.110.164244

Chakrabarti M, Klionsky DJ, Ray SK (2016) miR-30e blocks autophagy and acts synergistically with proanthocyanidin for inhibition of AVEN and BIRC6 to increase apoptosis in glioblastoma stem cells and glioblastoma SNB19 cells. PLoS One 11(7):e0158537. https://doi.org/10.1371/journal.pone.0158537

Lin H, Li HF, Chen HH, Lai PF, Juan SH, Chen JJ, Cheng CF (2014) Activating transcription factor 3 protects against pressure-overload heart failure via the autophagy molecule Beclin-1 pathway. Mol Pharmacol 85(5):682–691. https://doi.org/10.1124/mol.113.090092

Kalam K, Marwick TH (2013) Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer 49(13):2900–2909. https://doi.org/10.1016/j.ejca.2013.04.030

Abdel-Qadir H, Ong G, Fazelzad R, Amir E, Lee DS, Thavendiranathan P, Tomlinson G (2017) Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis. Ann Oncol 28(3):628–633. https://doi.org/10.1093/annonc/mdw671

Yun S, Vincelette ND, Abraham I (2015) Cardioprotective role of beta-blockers and angiotensin antagonists in early-onset anthracyclines-induced cardiotoxicity in adult patients: a systematic review and meta-analysis. Postgrad Med J 91(1081):627–633. https://doi.org/10.1136/postgradmedj-2015-133,535

Gujral DM, Lloyd G, Bhattacharyya S (2018) Effect of prophylactic betablocker or ACE inhibitor on cardiac dysfunction & heart failure during anthracycline chemotherapy +/- trastuzumab. Breast 37:64–71. https://doi.org/10.1016/j.breast.2017.10.010

Blaes AH, Gaillard P, Peterson BA, Yee D, Virnig B (2010) Angiotensin converting enzyme inhibitors may be protective against cardiac complications following anthracycline chemotherapy. Breast Cancer Res Treat 122(2):585–590. https://doi.org/10.1007/s10549-009-0730-5

Wittayanukorn S, Qian J, Westrick SC, Billor N, Johnson B, Hansen RA (2018) Prevention of trastuzumab and anthracycline-induced cardiotoxicity using angiotensin-converting enzyme inhibitors or beta-blockers in older adults with breast cancer. Am J Clin Oncol 41(9):909–918. https://doi.org/10.1097/coc.0000000000000389

Georgakopoulos P, Roussou P, Matsakas E, Karavidas A, Anagnostopoulos N, Marinakis T, Galanopoulos A, Georgiakodis F, Zimeras S, Kyriakidis M, Ahimastos A (2010) Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol 85(11):894–896. https://doi.org/10.1002/ajh.21840

Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, Morales-Ruiz M, Perea RJ, Monzo M, Esteve J (2013) Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am College Cardiol 61(23):2355–2362. https://doi.org/10.1016/j.jacc.2013.02.072

Janbabai G, Nabati M, Faghihinia M, Azizi S, Borhani S, Yazdani J (2017) Effect of enalapril on preventing anthracycline-induced cardiomyopathy. Cardiovasc Toxicol 17(2):130–139. https://doi.org/10.1007/s12012-016-9365-z

Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, Ganame J, Sebag IA, Agler DA, Badano LP, Banchs J, Cardinale D, Carver J, Cerqueira M, DeCara JM, Edvardsen T, Flamm SD, Force T, Griffin BP, Jerusalem G, Liu JE, Magalhaes A, Marwick T, Sanchez LY, Sicari R, Villarraga HR, Lancellotti P (2014) Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 27(9):911–939. https://doi.org/10.1016/j.echo.2014.07.012

Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, Martinelli G, Veglia F, Fiorentini C, Cipolla CM (2006) Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114(23):2474–2481. https://doi.org/10.1161/circulationaha.106.635144

Cardinale D, Ciceri F, Latini R, Franzosi MG, Sandri MT, Civelli M, Cucchi G, Menatti E, Mangiavacchi M, Cavina R, Barbieri E, Gori S, Colombo A, Curigliano G, Salvatici M, Rizzo A, Ghisoni F, Bianchi A, Falci C, Aquilina M, Rocca A, Monopoli A, Milandri C, Rossetti G, Bregni M, Sicuro M, Malossi A, Nassiacos D, Verusio C, Giordano M, Staszewsky L, Barlera S, Nicolis EB, Magnoli M, Masson S, Cipolla CM (2018) Anthracycline-induced cardiotoxicity: a multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial. Eur J Cancer 94:126–137. https://doi.org/10.1016/j.ejca.2018.02.005

Gupta V, Kumar Singh S, Agrawal V, Bali Singh T (2018) Role of ACE inhibitors in anthracycline-induced cardiotoxicity: A randomized, double-blind, placebo-controlled trial. Pediatr Blood Cancer 65(11):e27308. https://doi.org/10.1002/pbc.27308

Dlugosz-Danecka M, Gruszka AM, Szmit S, Olszanecka A, Ogorka T, Sobocinski M, Jaroszynski A, Krawczyk K, Skotnicki AB, Jurczak W (2018) Primary cardioprotection reduces mortality in lymphoma patients with increased risk of anthracycline cardiotoxicity, treated by R-CHOP regimen. Chemotherapy 63(4):238–245. https://doi.org/10.1159/000492942

Radulescu D, Buzdugan E, Ciuleanu TE, Todor N, Stoicescu L (2013) Can the epirubicin cardiotoxicity in cancer patients be prevented by angiotensin converting enzyme inhibitors? J BUON 18(4):1052–1057

Meattini I, Curigliano G, Terziani F, Becherini C, Airoldi M, Allegrini G, Amoroso D, Barni S, Bengala C, Guarneri V, Marchetti P, Martella F, Piovano P, Vannini A, Desideri I, Tarquini R, Galanti G, Barletta G, Livi L (2017) SAFE trial: an ongoing randomized clinical study to assess the role of cardiotoxicity prevention in breast cancer patients treated with anthracyclines with or without trastuzumab. Med Oncol 34(5):75. https://doi.org/10.1007/s12032-017-0938-x

Nakamae H, Tsumura K, Terada Y, Nakane T, Nakamae M, Ohta K, Yamane T, Hino M (2005) Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Cancer 104(11):2492–2498. https://doi.org/10.1002/cncr.21478

Cadeddu C, Piras A, Mantovani G, Deidda M, Dessi M, Madeddu C, Massa E, Mercuro G (2010) Protective effects of the angiotensin II receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early ventricular impairment. Am Heart J 160(3):487 e481–487 e487. https://doi.org/10.1016/j.ahj.2010.05.037

Dessi M, Piras A, Madeddu C, Cadeddu C, Deidda M, Massa E, Antoni G, Mantovani G, Mercuro G (2011) Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress and myocardial dysfunction. Exp Ther Med 2(5):1003–1009. https://doi.org/10.3892/etm.2011.305

Dessi M, Madeddu C, Piras A, Cadeddu C, Antoni G, Mercuro G, Mantovani G (2013) Long-term, up to 18 months, protective effects of the angiotensin II receptor blocker telmisartan on Epirubin-induced inflammation and oxidative stress assessed by serial strain rate. SpringerPlus 2(1):198. https://doi.org/10.1186/2193-1801-2-198

Mercuro G, Cadeddu C, Piras A, Dessi M, Madeddu C, Deidda M, Serpe R, Massa E, Mantovani G (2007) Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist 12(9):1124–1133. https://doi.org/10.1634/theoncologist.12-9-1124

Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, Gravdehaug B, von Knobelsdorff-Brenkenhoff F, Bratland A, Storas TH, Hagve TA, Rosjo H, Steine K, Geisler J, Omland T (2016) Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J 37(21):1671–1680. https://doi.org/10.1093/eurheartj/ehw022

Gulati G, Heck SL, Rosjo H, Ree AH, Hoffmann P, Hagve TA, Norseth J, Gravdehaug B, Steine K, Geisler J, Omland T (2017) Neurohormonal blockade and circulating cardiovascular biomarkers during anthracycline therapy in breast cancer patients: results from the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) study. J Am Heart Assoc 6(11). https://doi.org/10.1161/jaha.117.006513

Akpek M, Ozdogru I, Sahin O, Inanc M, Dogan A, Yazici C, Berk V, Karaca H, Kalay N, Oguzhan A, Ergin A (2015) Protective effects of spironolactone against anthracycline-induced cardiomyopathy. Eur J Heart Fail 17(1):81–89. https://doi.org/10.1002/ejhf.196

Davis MK, Virani SA (2016) Routine prophylactic cardioprotective therapy should not be given to all recipients of potentially cardiotoxic cancer chemotherapy. Can J Cardiol 32(7):926–930. https://doi.org/10.1016/j.cjca.2016.02.061

Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand JB, Ewer M, Fabian C, Hudson M, Jessup M, Jones LW, Ky B, Mayer EL, Moslehi J, Oeffinger K, Ray K, Ruddy K, Lenihan D (2017) Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 35(8):893–911. https://doi.org/10.1200/jco.2016.70.5400

Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A, Herrmann J, Porter C, Lyon AR, Lancellotti P, Patel A, DeCara J, Mitchell J, Harrison E, Moslehi J, Witteles R, Calabro MG, Orecchia R, de Azambuja E, Zamorano JL, Krone R, Iakobishvili Z, Carver J, Armenian S, Ky B, Cardinale D, Cipolla CM, Dent S, Jordan K (2020) Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol 31(2):171–190. https://doi.org/10.1016/j.annonc.2019.10.023

Jensen BV, Nielsen SL, Jensen TS (1997) Angiotensin-converting enzyme inhibitor in the treatment of epirubicin-induced dilated cardiomyopathy. Ugeskr Laeger 159(13):1945–1949

Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM (2010) Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 55(3):213–220. https://doi.org/10.1016/j.jacc.2009.03.095

Lipshultz SE, Lipsitz SR, Sallan SE, Simbre VC 2nd, Shaikh SL, Mone SM, Gelber RD, Colan SD (2002) Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer. J Clin Oncol 20(23):4517–4522. https://doi.org/10.1200/jco.2002.12.102

Jensen BV, Skovsgaard T, Nielsen SL (2002) Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients. Ann Oncol 13(5):699–709

Ohtani K, Fujino T, Ide T, Funakoshi K, Sakamoto I, Hiasa KI, Higo T, Kamezaki K, Akashi K, Tsutsui H (2019) Recovery from left ventricular dysfunction was associated with the early introduction of heart failure medical treatment in cancer patients with anthracycline-induced cardiotoxicity. Clin Res Cardiol 108(6):600–611. https://doi.org/10.1007/s00392-018-1386-0

Sheppard CE, Anwar M (2018) The use of sacubitril/valsartan in anthracycline-induced cardiomyopathy: a mini case series. J Oncol Pharm Pract. https://doi.org/10.1177/1078155218783238

Fadol AP (2018) Management of chemotherapy-induced left ventricular dysfunction and heart failure in patients with cancer while undergoing cancer treatment: the MD Anderson practice. Front Cardiovasc Med 5:24. https://doi.org/10.3389/fcvm.2018.00024

Guglin M, Krischer J, Tamura R, Fink A, Bello-Matricaria L, McCaskill-Stevens W, Munster PN (2019) Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer. J Am Coll Cardiol 73(22):2859–2868. https://doi.org/10.1016/j.jacc.2019.03.495

Heck SL, Gulati G, Hoffmann P, von Knobelsdorff-Brenkenhoff F, Storas TH, Ree AH, Gravdehaug B, Rosjo H, Steine K, Geisler J, Schulz-Menger J, Omland T (2018) Effect of candesartan and metoprolol on myocardial tissue composition during anthracycline treatment: the PRADA trial. Eur Heart J Cardiovasc Imaging 19(5):544–552. https://doi.org/10.1093/ehjci/jex159

McKay RR, Rodriguez GE, Lin X, Kaymakcalan MD, Hamnvik OP, Sabbisetti VS, Bhatt RS, Simantov R, Choueiri TK (2015) Angiotensin system inhibitors and survival outcomes in patients with metastatic renal cell carcinoma. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-14-2332