Sirtuins family as a target in endothelial cell dysfunction: implications for vascular ageing

Ahmed FW, Rider R, Glanville M, Narayanan K, Razvi S, Weaver JU (2016) Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study. Cardiovasc Diabetol 15:116. https://doi.org/10.1186/s12933-016-0413-6 Arunachalam G, Samuel SM, Marei I, Ding H, Triggle CR (2014) Metformin modulates hyperglycaemia-induced endothelial senescence and apoptosis through SIRT1. Br J Pharmacol 171:523–535. https://doi.org/10.1111/bph.12496 Arunachalam G, Lakshmanan AP, Samuel SM, Triggle CR, Ding H (2016) Molecular interplay between microRNA-34a and Sirtuin1 in hyperglycemia-mediated impaired angiogenesis in endothelial cells: effects of metformin. J Pharmacol Exp Ther 356:314–323. https://doi.org/10.1124/jpet.115.226894 Balestrieri ML et al (2008) High glucose downregulates endothelial progenitor cell number via SIRT1. Biochim Biophys Acta 1784:936–945. https://doi.org/10.1016/j.bbapap.2008.03.004 Balestrieri ML et al (2015) Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment. Diabetes 64:1395–1406. https://doi.org/10.2337/db14-1149 Boily G et al (2008) SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS ONE 3:e1759–e1759. https://doi.org/10.1371/journal.pone.0001759 Boini KM, Hussain T, Li PL, Koka S (2017) Trimethylamine-N-oxide instigates NLRP3 inflammasome activation and endothelial dysfunction. Cell Physiol Biochem 44:152–162. https://doi.org/10.1159/000484623 Boocock DJ et al (2007) Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev 16:1246–1252. https://doi.org/10.1158/1055-9965.EPI-07-0022 Brown VA et al (2010) Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 70:9003–9011. https://doi.org/10.1158/0008-5472.CAN-10-2364 Cacicedo JM, Gauthier MS, Lebrasseur NK, Jasuja R, Ruderman NB, Ido Y (2011) Acute exercise activates AMPK and eNOS in the mouse aorta. Am J Physiol Heart Circ Physiol 301:H1255–1265. https://doi.org/10.1152/ajpheart.01279.2010 Cao W, Dou Y, Li A (2018) Resveratrol boosts cognitive function by targeting SIRT1. Neurochem Res 43:1705–1713. https://doi.org/10.1007/s11064-018-2586-8 Cardus A, Uryga AK, Walters G, Erusalimsky JD (2013) SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence. Cardiovasc Res 97:571–579. https://doi.org/10.1093/cvr/cvs352 Cazzaniga A, Locatelli L, Castiglioni S, Maier JAM (2019) The dynamic adaptation of primary human endothelial cells to simulated microgravity. FASEB J 33:5957–5966. https://doi.org/10.1096/fj.201801586RR Chalkiadaki A, Guarente L (2012) High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction. Cell Metab 16:180–188. https://doi.org/10.1016/j.cmet.2012.07.003 Chan S-H et al (2018a) Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling. Redox Biol 14:116–125. https://doi.org/10.1016/j.redox.2017.08.016 Chan SH et al (2018b) Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling. Redox Biol 14:116–125. https://doi.org/10.1016/j.redox.2017.08.016 Cheang WS et al (2019) Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor delta. Pharmacol Res 139:384–394. https://doi.org/10.1016/j.phrs.2018.11.041 Chen J et al (2012) Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence. Am J Pathol 180:973–983. https://doi.org/10.1016/j.ajpath.2011.11.033 Chen Y, Fu LL, Wen X, Wang XY, Liu J, Cheng Y, Huang J (2014a) Sirtuin-3 (SIRT3), a therapeutic target with oncogenic and tumor-suppressive function in cancer. Cell Death Dis 5:e1047–e1047. https://doi.org/10.1038/cddis.2014.14 Chen Y, Wang H, Luo G, Dai X (2014b) SIRT4 inhibits cigarette smoke extracts-induced mononuclear cell adhesion to human pulmonary microvascular endothelial cells via regulating NF-κB activity. Toxicol Lett 226:320–327. https://doi.org/10.1016/j.toxlet.2014.02.022 Chen Z et al (2015) Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation 131:805–814. https://doi.org/10.1161/CIRCULATIONAHA.114.013675 Chen Y, Liu H, Zhang H, Liu E, Xu C-B, Su X (2016) The sirt1/NF-kB signaling pathway is involved in regulation of endothelin type B receptors mediated by homocysteine in vascular smooth muscle cells. Biomed Pharmacother 84:1979–1985. https://doi.org/10.1016/j.biopha.2016.11.011 Cheng J, Luo X, Huang Z, Chen L (2019) Apelin/APJ system: a potential therapeutic target for endothelial dysfunction-related diseases. J Cell Physiol 234:12149–12160. https://doi.org/10.1002/jcp.27942 Cheung TM, Yan JB, Fu JJ, Huang J, Yuan F, Truskey GA (2015) Endothelial cell senescence increases traction forces due to age-associated changes in the glycocalyx and SIRT1. Cell Mol Bioeng 8:63–75. https://doi.org/10.1007/s12195-014-0371-6 Chu H et al (2018) Resveratrol protects late endothelial progenitor cells from TNF-alpha-induced inflammatory damage by upregulating Kruppel-like factor-2. Mol Med Rep 17:5708–5715. https://doi.org/10.3892/mmr.2018.8621 Civitarese AE et al (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4:e76–e76. https://doi.org/10.1371/journal.pmed.0040076 Coletta C et al (2012) Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci USA 109:9161–9166. https://doi.org/10.1073/pnas.1202916109 Costa CdS et al (2010) SIRT1 transcription is decreased in visceral adipose tissue of morbidly obese patients with severe hepatic steatosis. Obes Surg 20:633–639. https://doi.org/10.1007/s11695-009-0052-z D’Onofrio N, Vitiello M, Casale R, Servillo L, Giovane A, Balestrieri ML (2015) Sirtuins in vascular diseases: emerging roles and therapeutic potential. Biochim Biophys Acta 1852:1311–1322. https://doi.org/10.1016/j.bbadis.2015.03.001 D'Onofrio N, Servillo L, Balestrieri ML (2018) SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection. Antioxid Redox Signal 28:711–732. https://doi.org/10.1089/ars.2017.7178 Dai H, Sinclair DA, Ellis JL, Steegborn C (2018) Sirtuin activators and inhibitors: promises, achievements, and challenges. Pharmacol Ther 188:140–154. https://doi.org/10.1016/j.pharmthera.2018.03.004 Das A et al (2018) Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging. Cell 173:74–89.e20. https://doi.org/10.1016/j.cell.2018.02.008 Delmas D, Aires V, Limagne E, Dutartre P, Mazué F, Ghiringhelli F, Latruffe N (2011) Transport, stability, and biological activity of resveratrol. Ann N Y Acad Sci 1215:48–59. https://doi.org/10.1111/j.1749-6632.2010.05871.x Ding M et al (2015) SIRT1 protects against myocardial ischemia-reperfusion injury via activating eNOS in diabetic rats. Cardiovasc Diabetol 14:143–143. https://doi.org/10.1186/s12933-015-0299-8 Eilken HM et al (2017) Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1. Nat Commu 8:1574. https://doi.org/10.1038/s41467-017-01738-3 Fernandes GFS, Silva GDB, Pavan AR, Chiba DE, Chin CM, Dos Santos JL (2017) Epigenetic regulatory mechanisms induced by resveratrol. Nutrients 9:1201. https://doi.org/10.3390/nu9111201 Förstermann U, Li H (2011) Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling. Br J Pharmacol 164:213–223. https://doi.org/10.1111/j.1476-5381.2010.01196.x Förstermann U, Münzel T (2006) Endothelial nitric oxide synthase in vascular disease. Circulation 113:1708–1714. https://doi.org/10.1161/CIRCULATIONAHA.105.602532 Fourny N, Lan C, Seree E, Bernard M, Desrois M (2019) Protective effect of resveratrol against ischemia-reperfusion injury via enhanced high energy compounds and eNOS-SIRT1 expression in type 2 diabetic female rat heart. Nutrients. https://doi.org/10.3390/nu11010105 Gambini J et al (2015) Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxid Med Cell Longev 2015:837042–837042. https://doi.org/10.1155/2015/837042 Gao J et al (2018) Loss of histone deacetylase 2 inhibits oxidative stress induced by high glucose via the HO-1/SIRT1 pathway in endothelial progenitor cells. Gene 678:1–7. https://doi.org/10.1016/j.gene.2018.07.072 Gerhardt H et al (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161:1163–1177. https://doi.org/10.1083/jcb.200302047 Gescher AJ, Steward WP (2003) Relationship between mechanisms, bioavailibility, and preclinical chemopreventive efficacy of resveratrol: a conundrum. Cancer Epidemiol Biomarkers Prev 12:953–957 Ghosh A, Gao L, Thakur A, Siu PM, Lai CWK (2017) Role of free fatty acids in endothelial dysfunction. J Biomed Sci 24:50. https://doi.org/10.1186/s12929-017-0357-5 Gomes BAQ et al (2018) Neuroprotective mechanisms of resveratrol in Alzheimer's disease: role of SIRT1. Oxid Med Cell Long 2018:8152373. https://doi.org/10.1155/2018/8152373 Gorenne I, Kumar S, Gray K, Figg N, Yu H, Mercer J, Bennett M (2013) Vascular smooth muscle cell sirtuin 1 protects against DNA damage and inhibits atherosclerosis. Circulation 127:386–396. https://doi.org/10.1161/CIRCULATIONAHA.112.124404 Grabowska W, Sikora E, Bielak-Zmijewska A (2017) Sirtuins, a promising target in slowing down the ageing process. Biogerontology 18:447–476. https://doi.org/10.1007/s10522-017-9685-9 Guarente L (2013) Calorie restriction and sirtuins revisited. Genes Dev 27:2072–2085. https://doi.org/10.1101/gad.227439.113 Guo Y et al (2018) Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells. Cardiovasc Res. https://doi.org/10.1093/cvr/cvy212 Guo J et al (2019) Endothelial SIRT6 is vital to prevent hypertension and associated cardiorenal injury through targeting Nkx3.2-GATA5. Signal Circ Res 124:1448–1461. https://doi.org/10.1161/circresaha.118.314032 Harsha N et al (2017) CR6-interacting factor 1 deficiency impairs vascular function by inhibiting the Sirt1-endothelial nitric oxide synthase pathway. Antioxid Redox Signal 27:234–249. https://doi.org/10.1089/ars.2016.6719 Hashimoto-Komatsu A, Hirase T, Asaka M, Node K (2011) Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells. Hypertens Res 34:949–956. https://doi.org/10.1038/hr.2011.64 He X, Zeng H, Roman RJ, Chen J-X (2018) Inhibition of prolyl hydroxylases alters cell metabolism and reverses pre-existing diastolic dysfunction in mice. Int J Cardiol 272:281–287. https://doi.org/10.1016/j.ijcard.2018.08.065 He X, Zeng H, Chen J-X (2019a) Emerging role of SIRT3 in endothelial metabolism, angiogenesis, and cardiovascular disease. J Cell Physiol 234:2252–2265. https://doi.org/10.1002/jcp.27200 He Y et al (2019b) Sitagliptin inhibits vascular inflammation via the SIRT6-dependent signaling pathway. Int Immunopharmacol 75:105805. https://doi.org/10.1016/j.intimp.2019.105805 Heath JM, Fernandez Esmerats J, Khambouneheuang L, Kumar S, Simmons R, Jo H (2018) Mechanosensitive microRNA-181b regulates aortic valve endothelial matrix degradation by targeting TIMP3. Cardiovasc Eng Technol 9:141–150. https://doi.org/10.1007/s13239-017-0296-z Heilbronn LK, Ravussin E (2003) Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr 78:361–369. https://doi.org/10.1093/ajcn/78.3.361 Herman AB, Autieri MV (2018) Cardiovascular disease, inflammation, and mRNA stability. Aging 10:3046–3047. https://doi.org/10.18632/aging.101619 Higashi Y, Yoshizumi M (2004) Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacol Ther 102:87–96. https://doi.org/10.1016/j.pharmthera.2004.02.003 Hsu PY, Lin WY, Lin RT, Juo SHH (2018) MicroRNA let-7g inhibits angiotensin II-induced endothelial senescence via the LOX-1-independent mechanism. Int J Mol Med 41:2243–2251. https://doi.org/10.3892/ijmm.2018.3416 Huang B, Zhang W, Wei L, Chen S, Wang T, Fu R (2018) Resveratrol down-regulates endothelin type B receptors in vascular smooth muscle cells via Sirt1/ERK1/2/NF-кB signaling pathways. Eur J Pharmacol 840:44–49. https://doi.org/10.1016/j.ejphar.2018.09.022 Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F (2018) Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol 100:1–19. https://doi.org/10.1016/j.vph.2017.05.005 Jaffe EA (1987) Cell biology of endothelial cells. Hum Pathol 18:234–239. https://doi.org/10.1016/S0046-8177(87)80005-9 Jang IA et al (2018) Effects of resveratrol on the renin-angiotensin system in the aging kidney. Nutrients. https://doi.org/10.3390/nu10111741 Jannin B, Menzel M, Berlot J-P, Delmas D, Lançon A, Latruffe N (2004) Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake. Biochem Pharmacol 68:1113–1118. https://doi.org/10.1016/j.bcp.2004.04.028 Jesko H, Strosznajder RP (2016) Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases. Folia Neuropathol 54:212–233 Jęśko H, Wencel P, Strosznajder RP, Strosznajder JB (2017) Sirtuins and their roles in brain aging and neurodegenerative disorders. Neurochem Res 42:876–890. https://doi.org/10.1007/s11064-016-2110-y Jiang T, Jiang D, Zhang L, Ding M, Zhou H (2019) Anagliptin ameliorates high glucose-induced endothelial dysfunction via suppression of NLRP3 inflammasome activation mediated by SIRT1. Mol Immunol 107:54–60. https://doi.org/10.1016/j.molimm.2019.01.006 Joshi S, Kar S, Kavdia M (2017) Computational analysis of interactions of oxidative stress and tetrahydrobiopterin reveals instability in eNOS coupling. Microvasc Res 114:114–128. https://doi.org/10.1016/j.mvr.2017.07.001 Karasawa T, Takahashi M (2017) Role of NLRP3 inflammasomes in atherosclerosis. J Atheroscler Thromb 24:443–451. https://doi.org/10.5551/jat.RV17001 Kassan M et al (2017) Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress. Sci Rep 7:42265. https://doi.org/10.1038/srep42265 Kato R et al (2016) Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease. Respir Res 17:139. https://doi.org/10.1186/s12931-016-0452-2 Kaur I, Rawal P, Rohilla S, Bhat MH, Sharma P, Siddiqui H, Kaur S (2018) Endothelial progenitor cells from aged subjects display decreased expression of sirtuin 1, angiogenic functions, and increased senescence. Cell Biol Int 42:1212–1220. https://doi.org/10.1002/cbin.10999 Ke Y et al (2018) Gut flora-dependent metabolite trimethylamine-N-oxide accelerates endothelial cell senescence and vascular aging through oxidative stress. Free Radical Biol Med 116:88–100. https://doi.org/10.1016/j.freeradbiomed.2018.01.007 Kida Y, Goligorsky MS (2016) Sirtuins, cell senescence, and vascular aging. Can J Cardiol 32:634–641. https://doi.org/10.1016/j.cjca.2015.11.022 Kim MY et al (2012) The PPARδ-mediated inhibition of angiotensin II-induced premature senescence in human endothelial cells is SIRT1-dependent. Biochem Pharmacol 84:1627–1634. https://doi.org/10.1016/j.bcp.2012.09.008 Kim DJ, Martinez-Lemus LA, Davis GE (2013) EB1, p150Glued, and Clasp1 control endothelial tubulogenesis through microtubule assembly, acetylation, and apical polarization. Blood 121:3521–3530. https://doi.org/10.1182/blood-2012-11-470179 Kim JS et al (2015) Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells. Am J Physiol Heart Circ Physiol 309:H425–433. https://doi.org/10.1152/ajpheart.00438.2014 Konukoglu D, Uzun H (2017) Endothelial dysfunction and hypertension. In: Islam MS (ed) Hypertension: from basic research to clinical practice. Springer, Cham, pp 511–540 Kuhnle G et al (2000) Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem Biophys Res Commun 272:212–217. https://doi.org/10.1006/bbrc.2000.2750 Kukkemane K, Jagota A (2019) Therapeutic effects of curcumin on age-induced alterations in daily rhythms of clock genes and Sirt1 expression in the SCN of male Wistar rats. Biogerontology 20:405–419. https://doi.org/10.1007/s10522-018-09794-y Kuno A, Tanno M, Horio Y (2015) The effects of resveratrol and SIRT1 activation on dystrophic cardiomyopathy. Ann N Y Acad Sci 1348:46–54. https://doi.org/10.1111/nyas.12812 Kutryb-Zajac B, Koszalka P, Slominska EM, Smolenski RT (2018) The effects of pro- and anti-atherosclerotic factors on intracellular nucleotide concentration in murine endothelial cells. Nucleosides Nucleotides Nucleic Acids. https://doi.org/10.1080/15257770.2018.1498513 Lai WK, Kan MY (2015) Homocysteine-induced endothelial dysfunction. Ann Nutr Metab 67:1–12. https://doi.org/10.1159/000437098 Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circ Res 100:782–794. https://doi.org/10.1161/01.RES.0000259593.07661.1e Lamichane S et al (2019) MHY2233 attenuates replicative cellular senescence in human endothelial progenitor cells via SIRT1 signaling. Oxid Med Cell Longev 2019:6492029–6492029. https://doi.org/10.1155/2019/6492029 Lee H-M, Kim J-J, Kim HJ, Shong M, Ku BJ, Jo E-K (2013) Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes 62:194–204. https://doi.org/10.2337/db12-0420 Lee S-H, Lee J-H, Lee H-Y, Min K-J (2019a) Sirtuin signaling in cellular senescence and aging. BMB Rep 52:24–34. https://doi.org/10.5483/BMBRep.2019.52.1.290 Lee SJ, Baek SE, Jang MA, Kim CD (2019b) SIRT1 inhibits monocyte adhesion to the vascular endothelium by suppressing Mac-1 expression on monocytes. Exp Mol Med 51:47. https://doi.org/10.1038/s12276-019-0239-x Lemarie CA et al (2011) Mthfr deficiency induces endothelial progenitor cell senescence via uncoupling of eNOS and downregulation of SIRT1. Am J Physiol Heart Circ Physiol 300:H745–753. https://doi.org/10.1152/ajpheart.00321.2010 Li L et al (2011) SIRT1 inhibits angiotensin II-induced vascular smooth muscle cell hypertrophy. Acta Biochim Biophys Sin 43:103–109. https://doi.org/10.1093/abbs/gmq104 Li W et al (2015a) Silent information regulator 1 (SIRT1) promotes the migration and proliferation of endothelial progenitor cells through the PI3K/Akt/eNOS signaling pathway. Int J Clin Exp Pathol 8:2274–2287 Li Z, Margariti A, Wu Y, Yang F, Hu J, Zhang L, Chen T (2015b) MicroRNA-199a induces differentiation of induced pluripotent stem cells into endothelial cells by targeting sirtuin. Mol Med Rep. https://doi.org/10.3892/mmr.2015.3845 Li Q et al (2016a) P66Shc-induced microRNA-34a causes diabetic endothelial dysfunction by downregulating Sirtuin1. Arterioscler Thromb Vasc Biol 36:2394–2403. https://doi.org/10.1161/atvbaha.116.308321 Li Y et al (2016b) SIRT1 inhibits inflammatory response partly through regulation of NLRP3 inflammasome in vascular endothelial cells. Mol Immunol 77:148–156. https://doi.org/10.1016/j.molimm.2016.07.018 Liao YC, Wang YS, Guo YC, Lin WL, Chang MH, Juo SH (2014) Let-7g improves multiple endothelial functions through targeting transforming growth factor-beta and SIRT-1 signaling. J Am Coll Cardiol 63:1685–1694. https://doi.org/10.1016/j.jacc.2013.09.069 Lipphardt M, Dihazi H, Muller GA, Goligorsky MS (2018a) Fibrogenic secretome of sirtuin 1-deficient endothelial cells: Wnt, Notch and Glycocalyx. Rheostat Front Physiol 9:7. https://doi.org/10.3389/fphys.2018.01325 Lipphardt M, Dihazi H, Müller GA, Goligorsky MS (2018b) Fibrogenic secretome of sirtuin 1-deficient endothelial cells: Wnt, Notch and Glycocalyx Rheostat. Front Physiol. https://doi.org/10.3389/fphys.2018.01325 Liu TF, Vachharajani VT, Yoza BK, McCall CE (2012) NAD+-dependent sirtuin 1 and 6 proteins coordinate a switch from glucose to fatty acid oxidation during the acute inflammatory response. J Biol Chem 287:25758–25769. https://doi.org/10.1074/jbc.M112.362343 Liu JN, Wu X, Wang X, Zhang Y, Bu PL, Zhang QY, Jiang F (2013) Global gene expression profiling reveals functional importance of Sirt2 in endothelial cells under oxidative stress. Int J Mol Sci 14:5633–5649. https://doi.org/10.3390/ijms14035633 Liu R, Liu H, Ha Y, Tilton RG, Zhang W (2014) Oxidative stress induces endothelial cell senescence via downregulation of Sirt6. Biomed Res Int 2014:902842. https://doi.org/10.1155/2014/902842 Liu Z, Wang J, Huang X, Li Z, Liu P (2016) Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice. Transl Res 172:18–29.e12. https://doi.org/10.1016/j.trsl.2016.02.005 Liu P et al (2018) Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation. Biochim Biophys Acta (BBA) 1864:764–777. https://doi.org/10.1016/j.bbadis.2017.12.027 Liu C et al (2019) Targeting pericyte-endothelial cell crosstalk by circular RNA-cPWWP2A inhibition aggravates diabetes-induced microvascular dysfunction. Proc Natl Acad Sci USA 116:7455–7464. https://doi.org/10.1073/pnas.1814874116 Lu Y et al (2018) Protective effects of Danzhi jiangtang capsule on vascular endothelial damages induced by high-fat diet and palmitic acid. Biomed Pharmacother 107:1631–1640. https://doi.org/10.1016/j.biopha.2018.08.129 Luo X, Hu Y, He S, Ye Q, Lv Z, Liu J, Chen X (2019a) Dulaglutide inhibits high glucose-induced endothelial dysfunction and NLRP3 inflammasome activation. Arch Biochem Biophys 671:203–209. https://doi.org/10.1016/j.abb.2019.07.008 Luo Y, Lu S, Ai Q, Zhou P, Qin M, Sun G, Sun X (2019b) SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of total aralosides of Aralia elata (Miq) Seem against high-fat diet-induced atherosclerosis in ApoE-/- mice. PTR Phytotherapy Res. https://doi.org/10.1002/ptr.6269 Marier J-F, Vachon P, Gritsas A, Zhang J, Moreau J-P, Ducharme MP (2002) Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model. J Pharmacol Exp Ther 302:369–373. https://doi.org/10.1124/jpet.102.033340 Marton O et al (2010) Aging and exercise affect the level of protein acetylation and SIRT1 activity in cerebellum of male rats. Biogerontology 11:679–686. https://doi.org/10.1007/s10522-010-9279-2 Masaki T, Sawamura T (2006) Endothelin and endothelial dysfunction. Proc Jpn Acad Series B 82:17–24 Mattagajasingh I et al (2007) SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci 104:14855–14860. https://doi.org/10.1073/pnas.0704329104 Mercken EM et al (2014) SIRT1 but not its increased expression is essential for lifespan extension in caloric-restricted mice. Aging Cell 13:193–196. https://doi.org/10.1111/acel.12151 Miksits M et al (2005) Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1. Xenobiotica 35:1101–1119. https://doi.org/10.1080/00498250500354253 Ming G-f, Wu K, Hu K, Chen Y, Xiao J (2016) NAMPT regulates senescence, proliferation, and migration of endothelial progenitor cells through the SIRT1 AS lncRNA/miR-22/SIRT1 pathway. Biochem Biophys Res Commun 478:1382–1388. https://doi.org/10.1016/j.bbrc.2016.08.133 Miyashita H et al (2012) Angiogenesis inhibitor vasohibin-1 enhances stress resistance of endothelial cells via induction of SOD2 and SIRT1. PLoS ONE 7:12. https://doi.org/10.1371/journal.pone.0046459 Moriya J, Minamino T (2017) Angiogenesis, cancer, and vascular aging. Front Cardiovasc Med. https://doi.org/10.3389/fcvm.2017.00065 Mortuza R, Feng B, Chakrabarti S (2015) SIRT1 reduction causes renal and retinal injury in diabetes through endothelin 1 and transforming growth factor β1. J Cell Mol Med 19:1857–1867. https://doi.org/10.1111/jcmm.12557 Mudau M, Genis A, Lochner A, Strijdom H (2012) Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr 23:222–231. https://doi.org/10.5830/CVJA-2011-068 Nafisa A et al (2018) Endothelial function and dysfunction: impact of metformin. Pharmacol Ther 192:150–162. https://doi.org/10.1016/j.pharmthera.2018.07.007 Nakagawa T, Lomb DJ, Haigis MC, Guarente L (2009) SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137:560–570. https://doi.org/10.1016/j.cell.2009.02.026 Ong AT, Aoki J, Kutryk MJ, Serruys PW (2005) How to accelerate the endothelialization of stents. Arch Mal Coeur Vaiss 98:123–126 Ota H, Akishita M, Eto M, Iijima K, Kaneki M, Ouchi Y (2007) Sirt1 modulates premature senescence-like phenotype in human endothelial cells. J Mol Cell Cardiol 43:571–579. https://doi.org/10.1016/j.yjmcc.2007.08.008 Ota H et al (2010) Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler Thromb Vasc Biol 30:2205–2211. https://doi.org/10.1161/atvbaha.110.210500 Pacholec M et al (2010) SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 285:8340–8351. https://doi.org/10.1074/jbc.M109.088682 Pan F et al (2016) MicroRNA-200a is up-regulated in aged rats with erectile dysfunction and could attenuate endothelial function via SIRT1 inhibition. Asian J Androl 18:74–79. https://doi.org/10.4103/1008-682x.154991 Peltz L et al (2012) Resveratrol exerts dosage and duration dependent effect on human mesenchymal stem cell development. PLoS ONE 7:e37162–e37162. https://doi.org/10.1371/journal.pone.0037162 Piao S et al (2018) CR6 interacting factor 1 deficiency promotes endothelial inflammation by SIRT1 downregulation. PLoS ONE 13:16. https://doi.org/10.1371/journal.pone.0192693 Piqueras L et al (2007) Activation of PPARβ/δ; induces endothelial cell proliferation and angiogenesis. Arterioscler Thromb Vasc Biol 27:63–69. https://doi.org/10.1161/01.ATV.0000250972.83623.61 Qiu Y, Lai H, Huang Y, Hong L, Wang H, Tao Y (2016) Effect of shear force on SIRT4 in LPS-injured human umbilical vein endothelial cells. Int J Clin Exp Pathol 9:4921–4930 Redman LM, Smith SR, Burton JH, Martin CK, Il'yasova D, Ravussin E (2018) Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab 27:805–815.e804. https://doi.org/10.1016/j.cmet.2018.02.019 Rocha B et al (2018) Energy restriction, exercise and atorvastatin treatment improve endothelial dysfunction and inhibit miRNA-155 in the erectile tissue of the aged rat. Nutr Metab 15:12. https://doi.org/10.1186/s12986-018-0265-z Rokutanda T, Izumiya Y, Araki S, Hanatani S, Bober E, Braun T, Ogawa H (2012) Abstract 10980: Sirt7 regulates endothelial cell functions and promotes angiogenic response in mice model of hindlimb ischemia. Circulation 126:A10980–A10980. https://doi.org/10.1161/circ.126.suppl_21.A10980 Salani D, Taraboletti G, Rosanò L, Di Castro V, Borsotti P, Giavazzi R, Bagnato A (2000) Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Am J Pathol 157:1703–1711. https://doi.org/10.1016/S0002-9440(10)64807-9 Salmito FTS, de Oliveira Neves FM, Meneses GC, de Almeida LR, Martins AMC, Libório AB (2015) Glycocalyx injury in adults with nephrotic syndrome: association with endothelial function. Clin Chim Acta 447:55–58. https://doi.org/10.1016/j.cca.2015.05.013 Sidorova-Darmos E et al (2014) Differential expression of sirtuin family members in the developing, adult, and aged rat brain. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2014.00333 Sieve I, Münster-Kühnel AK, Hilfiker-Kleiner D (2018) Regulation and function of endothelial glycocalyx layer in vascular diseases. Vascul Pharmacol 100:26–33. https://doi.org/10.1016/j.vph.2017.09.002 Smoliga JM, Blanchard O (2014) Enhancing the delivery of resveratrol in humans: if low bioavailability is the problem, what is the solution? Molecules 19:17154–17172. https://doi.org/10.3390/molecules191117154 Smoliga JM, Colombo ES, Campen MJ (2013) A healthier approach to clinical trials evaluating resveratrol for primary prevention of age-related diseases in healthy populations. Aging (Albany NY) 5:495–506. https://doi.org/10.18632/aging.100579 Someya S et al (2010) Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143:802–812. https://doi.org/10.1016/j.cell.2010.10.002 Song X, Yang B, Qiu F, Jia M, Fu G (2017) High glucose and free fatty acids induce endothelial progenitor cell senescence via PGC-1alpha/SIRT1 signaling pathway. Cell Biol Int 41:1146–1159. https://doi.org/10.1002/cbin.10833 Sorrentino SA et al (2007) Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 116:163–173. https://doi.org/10.1161/circulationaha.106.684381 Sosnowska B, Mazidi M, Penson P, Gluba-Brzózka A, Rysz J, Banach M (2017) The sirtuin family members SIRT1, SIRT3 and SIRT6: their role in vascular biology and atherogenesis. Atherosclerosis 265:275–282. https://doi.org/10.1016/j.atherosclerosis.2017.08.027 Stocco B, Toledo K, Salvador M, Paulo M, Koyama N, Torqueti Toloi MR (2012) Dose-dependent effect of resveratrol on bladder cancer cells: chemoprevention and oxidative stress. Maturitas 72:72–78. https://doi.org/10.1016/j.maturitas.2012.02.004 Summerhill V, Karagodin V, Grechko A, Myasoedova V, Orekhov A (2018) Vasculoprotective role of olive oil compounds via modulation of oxidative stress in atherosclerosis. Front Cardiovasc Med. https://doi.org/10.3389/fcvm.2018.00188 Sun L, Bai Y, Du G (2009) Endothelial dysfunction: an obstacle of therapeutic angiogenesis. Ageing Res Rev 8:306–313. https://doi.org/10.1016/j.arr.2009.04.003 Sun S et al (2020) Vascular endothelium-targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model. Sci Adv. https://doi.org/10.1126/sciadv.aay5556 Takizawa Y et al (2013) Up-regulation of endothelial nitric oxide synthase (eNOS), silent mating type information regulation 2 homologue 1 (SIRT1) and autophagy-related genes by repeated treatments with resveratrol in human umbilical vein endothelial cells. Br J Nutr 110:2150–2155. https://doi.org/10.1017/S0007114513001670 Tang X, Chen XF, Chen HZ, Liu DP (2017) Mitochondrial sirtuins in cardiometabolic diseases. Clin Sci (London, England) 131:2063–2078. https://doi.org/10.1042/cs20160685 Tao Y, Huang C, Huang Y, Hong L, Wang H, Zhou Z, Qiu Y (2015) SIRT4 suppresses inflammatory responses in human umbilical vein endothelial cells. Cardiovasc Toxicol 15:217–223. https://doi.org/10.1007/s12012-014-9287-6 Tao Y, Yu S, Chao M, Wang Y, Xiong J, Lai H (2019) SIRT4 suppresses the PI3K/Akt/NF-κB signaling pathway and attenuates HUVEC injury induced by oxLDL. Mol Med Rep 19:4973–4979. https://doi.org/10.3892/mmr.2019.10161 Tasatargil A, Tanriover G, Barutcigil A, Turkmen E (2018) Protective effect of resveratrol on methylglyoxal-induced endothelial dysfunction in aged rats. Aging Clin Exp Res. https://doi.org/10.1007/s40520-018-0986-x Tennen RI, Berber E, Chua KF (2010) Functional dissection of SIRT6: Identification of domains that regulate histone deacetylase activity and chromatin localization. Mech Ageing Dev 131:185–192. https://doi.org/10.1016/j.mad.2010.01.006 Thangjam GS et al (2016) Hsp90 inhibition suppresses NF-kappa B transcriptional activation via Sirt-2 in human lung microvascular endothelial cells. Am J Physiol-Lung Cell Mol Physiol 310:L964–L974. https://doi.org/10.1152/ajplung.00054.2016 Thompson AM, Wagner R, Rzucidlo EM (2014) Age-related loss of SirT1 expression results in dysregulated human vascular smooth muscle cell function. Am J Physiol Heart Circ Physiol 307:H533–H541. https://doi.org/10.1152/ajpheart.00871.2013 Toiber D, Sebastian C, Mostoslavsky R (2011) Characterization of nuclear sirtuins: molecular mechanisms and physiological relevance. Handb Exp Pharmacol 206:189–224. https://doi.org/10.1007/978-3-642-21631-2_9 Trujillo-Gonzalez I et al (2018) microRNA-129-5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex. FASEB J. https://doi.org/10.1096/fj.201801094RR Urpí-Sardà M, Jáuregui O, Lamuela-Raventós RM, Jaeger W, Miksits M, Covas M-I, Andres-Lacueva C (2005) Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry. Anal Chem 77:3149–3155. https://doi.org/10.1021/ac0484272 Vachharajani VT, Liu T, Wang X, Hoth JJ, Yoza BK, McCall CE (2016) Sirtuins Link Inflammation and Metabolism. J Immunol Res 2016:10. https://doi.org/10.1155/2016/8167273 Vanhoutte PM (1997) Endothelial dysfunction and atherosclerosis. Eur Heart J 18:19–29. https://doi.org/10.1093/eurheartj/18.suppl_E.19 Vassallo PF et al (2014) Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression. Blood 123:2116–2126. https://doi.org/10.1182/blood-2013-02-484956 Vikram A, Kim YR, Kumar S, Li Q, Kassan M, Jacobs JS, Irani K (2016) Vascular microRNA-204 is remotely governed by the microbiome and impairs endothelium-dependent vasorelaxation by downregulating Sirtuin1. Nat Commun 7:12565. https://doi.org/10.1038/ncomms12565 Villalba JM, Alcaín FJ (2012) Sirtuin activators and inhibitors. BioFactors (Oxford, England) 38:349–359. https://doi.org/10.1002/biof.1032 Voghel G et al (2010) Endogenous oxidative stress prevents telomerase-dependent immortalization of human endothelial cells. Mech Ageing Dev 131:354–363. https://doi.org/10.1016/j.mad.2010.04.004 Walle T, Walle UK, Sedmera D, Klausner M (2006) Benzo[A]pyrene-induced oral carcinogenesis and chemoprevention: studies in bioengineered human tissue. Drug Metab Dispos 34:346–350. https://doi.org/10.1124/dmd.105.007948 Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Förstermann U (2002) Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 106:1652–1658. https://doi.org/10.1161/01.cir.0000029925.18593.5c Wan Y-Z et al (2014) SIRT1-mediated epigenetic downregulation of plasminogen activator inhibitor-1 prevents vascular endothelial replicative senescence. Aging Cell 13:890–899. https://doi.org/10.1111/acel.12247 Wang W et al (2019) Hydroxytyrosol NO regulates oxidative stress and NO production through SIRT1 in diabetic mice and vascular endothelial cells. Phytomedicine 52:206–215. https://doi.org/10.1016/j.phymed.2018.09.208 Wątroba M, Szukiewicz D (2016) The role of sirtuins in aging and age-related diseases. Adv Med Sci 61:52–62. https://doi.org/10.1016/j.advms.2015.09.003 Wenzel E, Somoza V (2005) Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res 49:472–481. https://doi.org/10.1002/mnfr.200500010 Winnik S, Auwerx J, Sinclair DA, Matter CM (2015) Protective effects of sirtuins in cardiovascular diseases: from bench to bedside. Eur Heart J 36:3404–3412. https://doi.org/10.1093/eurheartj/ehv290 Wu H, Chen Z, Chen JZ, Xie J, Xu B (2018) Resveratrol improves tube formation in AGE-induced late endothelial progenitor cells by suppressing syndecan-4 shedding. Oxid Med Cell Long 2018:9045976. https://doi.org/10.1155/2018/9045976 Xia N et al (2010) Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. J Pharmacol Exp Therap 335:149–154. https://doi.org/10.1124/jpet.110.168724 Xia N et al (2013) Role of SIRT1 and FOXO factors in eNOS transcriptional activation by resveratrol. Nitric Oxide 32:29–35. https://doi.org/10.1016/j.niox.2013.04.001 Xia N, Forstermann U, Li H (2014a) Resveratrol and endothelial nitric oxide. Molecules (Basel, Switzerland) 19:16102–16121. https://doi.org/10.3390/molecules191016102 Xia N, Förstermann U, Li H (2014b) Resveratrol and endothelial nitric oxide. Molecules 19:16102–16121. https://doi.org/10.3390/molecules191016102 Xia N, Daiber A, Forstermann U, Li H (2017) Antioxidant effects of resveratrol in the cardiovascular system. Br J Pharmacol 174:1633–1646. https://doi.org/10.1111/bph.13492 Xing S-S, Li J, Chen L, Yang Y-F, He P-L, Li J, Yang J (2018) Salidroside attenuates endothelial cellular senescence via decreasing the expression of inflammatory cytokines and increasing the expression of SIRT3. Mech Ageing Dev 175:1–6. https://doi.org/10.1016/j.mad.2017.12.005 Xu Z, Zhang L, Fei X, Yi X, Li W, Wang Q (2014) The miR-29b–Sirt1 axis regulates self-renewal of mouse embryonic stem cells in response to reactive oxygen species. Cell Signal 26:1500–1505. https://doi.org/10.1016/j.cellsig.2014.03.010 Xu S et al (2016) SIRT6 protects against endothelial dysfunction and atherosclerosis in mice. Aging 8:1064–1082. https://doi.org/10.18632/aging.100975 Yang F et al (2019) Metformin Inhibits the NLRP3 Inflammasome via AMPK/mTOR-dependent effects in diabetic cardiomyopathy. Int J Biol Sci 15:1010–1019. https://doi.org/10.7150/ijbs.29680 Yang J, Wang N, Li J, Zhang J, Feng P (2010) Effects of resveratrol on NO secretion stimulated by insulin and its dependence on SIRT1 in high glucose cultured endothelial cells. Endocrine 37:365–372. https://doi.org/10.1007/s12020-010-9314-8 Yang N-C, Song T-Y, Chang Y-Z, Chen M-Y, Hu M-L (2015) Up-regulation of nicotinamide phosphoribosyltransferase and increase of NAD+ levels by glucose restriction extend replicative lifespan of human fibroblast Hs68 cells. Biogerontology 16:31–42. https://doi.org/10.1007/s10522-014-9528-x Yao F et al (2019) The protective effect of hydroxytyrosol acetate against inflammation of vascular endothelial cells partly through the SIRT6-mediated PKM2 signaling pathway. Food Funct 10:5789–5803. https://doi.org/10.1039/c9fo00586b Yin W-L, Yin W-G, Huang B-S, Wu L-X (2019) LncRNA SNHG12 inhibits miR-199a to upregulate SIRT1 to attenuate cerebral ischemia/reperfusion injury through activating AMPK signaling pathway. Neurosci Lett 690:188–195. https://doi.org/10.1016/j.neulet.2018.08.026 Yu B-B et al (2019) Mitochondrial dysfunction-mediated decline in angiogenic capacity of endothelial progenitor cells is associated with capillary rarefaction in patients with hypertension via downregulation of CXCR4/JAK2/SIRT5 signaling. EBioMedicine 42:64–75. https://doi.org/10.1016/j.ebiom.2019.03.031 Yuan Q et al (2014) Regulation of endothelial progenitor cell differentiation and function by dimethylarginine dimethylaminohydrolase 2 in an asymmetric dimethylarginine-independent manner. Cell Biol Int 38:1013–1022. https://doi.org/10.1002/cbin.10288 Yuan Y, Cruzat VF, Newsholme P, Cheng J, Chen Y, Lu Y (2016) Regulation of SIRT1 in aging: roles in mitochondrial function and biogenesis. Mech Ageing Dev 155:10–21. https://doi.org/10.1016/j.mad.2016.02.003 Zhai J, Qu X, Zhang Y, Gao H, Tao L, Song Y, Zhang S (2019) Salvianolic acid inhibits the effects of high glucose on vascular endothelial dysfunction by modulating the Sirt1-eNOS pathway. J Biochem Mol Toxicol 33:e22245 Zhang L et al (2014) MiR-132 inhibits expression of SIRT1 and induces pro-inflammatory processes of vascular endothelial inflammation through blockade of the SREBP-1c metabolic pathway. Cardiovasc Drugs Ther 28:303–311. https://doi.org/10.1007/s10557-014-6533-x Zhang E, Guo Q, Gao H, Xu R, Teng S, Wu Y (2015) Metformin and resveratrol inhibited high glucose-induced metabolic memory of endothelial senescence through SIRT1/p300/p53/p21 pathway. PLoS ONE 10:e0143814–e0143814. https://doi.org/10.1371/journal.pone.0143814 Zhang J, Wang C, Nie H, Wu D, Ying W (2016) SIRT2 plays a significant role in maintaining the survival and energy metabolism of PIEC endothelial cells. Int J Physiol Pathophysiol Pharmacol 8:120–127 Zhang H-n, Xu Q-q, Thakur A, Alfred MO, Chakraborty M, Ghosh A, Yu X-b (2018a) Endothelial dysfunction in diabetes and hypertension: role of microRNAs and long non-coding RNAs Life. Sciences 213:258–268. https://doi.org/10.1016/j.lfs.2018.10.028 Zhang X, Sun D, Song JW, Zullo J, Lipphardt M, Coneh-Gould L, Goligorsky MS (2018b) Endothelial cell dysfunction and glycocalyx: a vicious circle Matrix. Biology 71–72:421–431. https://doi.org/10.1016/j.matbio.2018.01.026 Zhang C, Abdukerim M, Abilailieti M, Tang L, Ling Y, Pan S (2019) The protective effects of orexin a against high glucose-induced activation of NLRP3 inflammasome in human vascular endothelial cells. Arch Biochem Biophys. https://doi.org/10.1016/j.abb.2019.07.017 Zhao T, Li J, Chen AF (2010) MicroRNA-34a induces endothelial progenitor cell senescence and impedes its angiogenesis via suppressing silent information regulator 1. Am J Physiol Endocrinol Metab 299:E110–E116. https://doi.org/10.1152/ajpendo.00192.2010 Zhao Y, Vanhoutte PM, Leung SWS (2015) Vascular nitric oxide: beyond eNOS. J Pharmacol Sci 129:83–94. https://doi.org/10.1016/j.jphs.2015.09.002 Zu Y et al (2010) SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells. Circ Res 106:1384–1393. https://doi.org/10.1161/CIRCRESAHA.109.215483