Molecular mechanisms and genetic regulation in atherosclerosis

IJC Heart and Vasculature - Tập 21 - Trang 36-44 - 2018
Ampadu-Okyere Jackson1,2, Mugwaneza Annick Regine1,2, Chakrabarti Subrata3, Shiyin Long4
1Research lab of translational medicine, Medical school, University of South China, Hengyang, Hunan Province 421001, China
2International college, University of South China, Hengyang, Hunan Province 421001, China
3Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada
4Department of Biochemistry and Molecular Biology, University of South China, Hengyang, Hunan Province 421001, China

Tài liệu tham khảo

Chen, 2016, Carotid intima-media thickness and arterial stiffness and the risk of atrial fibrillation: the atherosclerosis risk in communities (ARIC) study, multi-ethnic study of atherosclerosis (MESA), and the Rotterdam study, J. Am. Heart Assoc., 5, 10.1161/JAHA.115.002907 Tomiyama, 2018, Longitudinal association among endothelial function, arterial stiffness and subclinical organ damage in hypertension, Int. J. Cardiol., 253, 161, 10.1016/j.ijcard.2017.11.022 Baragetti, 2018, Disease trends over time and CD4(+)CCR5(+) T-cells expansion predict carotid atherosclerosis development in patients with systemic lupus erythematosus, Nutr. Metab. Cardiovasc. Dis., 28, 53, 10.1016/j.numecd.2017.09.001 Ammirati, 2014, Cardiometabolic and immune factors associated with increased common carotid artery intima-media thickness and cardiovascular disease in patients with systemic lupus erythematosus, Nutr. Metab. Cardiovasc. Dis., 24, 751, 10.1016/j.numecd.2014.01.006 Seneviratne, 2017, Interferon regulatory factor 5 controls necrotic core formation in atherosclerotic lesions by impairing efferocytosis, Circulation, 136, 1140, 10.1161/CIRCULATIONAHA.117.027844 Chen, 2015, Endothelial-to-mesenchymal transition drives atherosclerosis progression, J. Clin. Invest., 125, 4514, 10.1172/JCI82719 Evrard, 2016, Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability, Nat. Commun., 7, 10.1038/ncomms11853 Sato, 2018, Adropin contributes to anti-atherosclerosis by suppressing monocyte-endothelial cell adhesion and smooth muscle cell proliferation, Int. J. Mol. Sci., 19, 10.3390/ijms19051293 Chen, 2018, SHP2 inhibitor PHPS1 protects against atherosclerosis by inhibiting smooth muscle cell proliferation, BMC Cardiovasc. Disord., 18, 72, 10.1186/s12872-018-0816-2 Parahuleva, 2018, MicroRNA expression profile of human advanced coronary atherosclerotic plaques, Sci. Rep., 8, 7823, 10.1038/s41598-018-25690-4 Horio, 2014, Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression, Arterioscler. Thromb. Vasc. Biol., 34, 790, 10.1161/ATVBAHA.113.303116 Zhou, 2018, Histamine H1 type receptor antagonist loratadine ameliorates oxidized LDL induced endothelial dysfunction, Biomed Pharmacother, 106, 1448, 10.1016/j.biopha.2018.07.025 Yao, 2015, Tetrahydroxystilbene glucoside improves TNF-alpha-induced endothelial dysfunction: involvement of TGFbeta/Smad pathway and inhibition of vimentin expression, Am. J. Chin. Med., 43, 183, 10.1142/S0192415X15500123 Zhang, 2018, The alpha1,3-fucosyltransferase FUT7 regulates IL-1beta-induced monocyte-endothelial adhesion via fucosylation of endomucin, Life Sci., 192, 231, 10.1016/j.lfs.2017.11.017 Zhang, 2014, TNF-alpha promotes early atherosclerosis by increasing transcytosis of LDL across endothelial cells: crosstalk between NF-kappaB and PPAR-gamma, J. Mol. Cell. Cardiol., 72, 85, 10.1016/j.yjmcc.2014.02.012 Dimitriadis, 2018, Chemerin induces endothelial cell inflammation: activation of nuclear factor-kappa beta and monocyte-endothelial adhesion, Oncotarget, 9, 16678, 10.18632/oncotarget.24659 Yang, 2017, Macrophage-derived foam cells impair endothelial barrier function by inducing endothelial-mesenchymal transition via CCL-4, Int. J. Mol. Med., 40, 558, 10.3892/ijmm.2017.3034 Feng, 2017, Apolipoprotein A1 inhibits the TGF-beta1-induced endothelial-to-mesenchymal transition of human coronary artery endothelial cells, Cardiology, 137, 179, 10.1159/000464321 Kim, 2013, The effect of oxidized low-density lipoprotein (ox-LDL) on radiation-induced endothelial-to-mesenchymal transition, Int. J. Radiat. Biol., 89, 356, 10.3109/09553002.2013.763193 Yu, 2017, High glucose induced endothelial to mesenchymal transition in human umbilical vein endothelial cell, Exp. Mol. Pathol., 102, 377, 10.1016/j.yexmp.2017.03.007 Busnelli, 2017, Liver-specific deletion of the Plpp3 gene alters plasma lipid composition and worsens atherosclerosis in apoE(−/−) mice, Sci. Rep., 7, 10.1038/srep44503 Rahman, 2017, Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study, Lipids Health Dis., 16, 81, 10.1186/s12944-017-0470-1 Panchatcharam, 2014, Mice with targeted inactivation of ppap2b in endothelial and hematopoietic cells display enhanced vascular inflammation and permeability, Arterioscler. Thromb. Vasc. Biol., 34, 837, 10.1161/ATVBAHA.113.302335 Yang, 2016, SIRT3 deficiency induces endothelial insulin resistance and blunts endothelial-dependent vasorelaxation in mice and human with obesity, Sci. Rep., 6 Liu, 2016, Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice, Transl. Res., 172, 18, 10.1016/j.trsl.2016.02.005 Akhtar, 2015, Endothelial hypoxia-inducible factor-1alpha promotes atherosclerosis and monocyte recruitment by upregulating microRNA-19a, Hypertension, 66, 1220, 10.1161/HYPERTENSIONAHA.115.05886 Shibata, 2007, Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) activation and lectin-like oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells, Atherosclerosis, 193, 20, 10.1016/j.atherosclerosis.2006.08.011 Minamino, 2003, Endothelial cell senescence in human atherosclerosis: role of telomeres in endothelial dysfunction, J. Cardiol., 41, 39 Wang, 2015, Vascular smooth muscle cell senescence promotes atherosclerosis and features of plaque vulnerability, Circulation, 132, 1909, 10.1161/CIRCULATIONAHA.115.016457 Kim, 2018, Gingerenone a attenuates monocyte-endothelial adhesion via suppression of I kappa B kinase phosphorylation, J. Cell. Biochem., 119, 260, 10.1002/jcb.26138 Del Toro, 2016, Nestin(+) cells direct inflammatory cell migration in atherosclerosis, Nat. Commun., 7, 10.1038/ncomms12706 Qian, 2016, Deletion of P2Y2 receptor reveals a role for lymphotoxin-alpha in fatty streak formation, Vasc. Pharmacol., 85, 11, 10.1016/j.vph.2016.06.001 Buhrmann, 2017, Resveratrol downregulates inflammatory pathway activated by lymphotoxin alpha (TNF-beta) in articular chondrocytes: comparison with TNF-alpha, PLoS One, 12, 10.1371/journal.pone.0186993 Feng, 2017, Mechanical activation of hypoxia-inducible factor 1alpha drives endothelial dysfunction at atheroprone sites, Arterioscler. Thromb. Vasc. Biol., 37, 2087, 10.1161/ATVBAHA.117.309249 Liu, 2016, Smooth muscle hypoxia-inducible factor 1alpha links intravascular pressure and atherosclerosis—brief report, Arterioscler. Thromb. Vasc. Biol., 36, 442, 10.1161/ATVBAHA.115.306861 Jiang, 2016, The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia, Sci. Rep., 6 Sun, 1998, Influence of genotype at the low density lipoprotein (LDL) receptor gene locus on the clinical phenotype and response to lipid-lowering drug therapy in heterozygous familial hypercholesterolaemia. The Familial Hypercholesterolaemia Regression Study Group, Atherosclerosis, 136, 175, 10.1016/S0021-9150(97)00181-0 Tada, 2016, Lipoprotein(a) in familial hypercholesterolemia with proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutations, Circ. J., 80, 512, 10.1253/circj.CJ-15-0999 Fairoozy, 2017, The genetic spectrum of familial hypercholesterolemia (FH) in the Iranian population, Sci. Rep., 7, 10.1038/s41598-017-17181-9 Di Taranto, 2017, Identification and in vitro characterization of two new PCSK9 gain of function variants found in patients with familial hypercholesterolemia, Sci. Rep., 7, 10.1038/s41598-017-15543-x Cohen, 2005, Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9, Nat. Genet., 37, 161, 10.1038/ng1509 Powell-Braxton, 1998, A mouse model of human familial hypercholesterolemia: markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet, Nat. Med., 4, 934, 10.1038/nm0898-934 Tang, 2017, New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-kappaB pathway, Atherosclerosis, 262, 113, 10.1016/j.atherosclerosis.2017.04.023 Bernelot Moens, 2017, PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia, Eur. Heart J., 38, 1584, 10.1093/eurheartj/ehx002 Zhao, 2006, Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote, Am. J. Hum. Genet., 79, 514, 10.1086/507488 Hallman, 2007, Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from the Bogalusa heart study), Am. J. Cardiol., 100, 69, 10.1016/j.amjcard.2007.02.057 Hooper, 2007, The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population, Atherosclerosis, 193, 445, 10.1016/j.atherosclerosis.2006.08.039 Murphy, 2008, High-density lipoprotein reduces the human monocyte inflammatory response, Arterioscler. Thromb. Vasc. Biol., 28, 2071, 10.1161/ATVBAHA.108.168690 Lawn, 1999, The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway, J. Clin. Invest., 104, R25, 10.1172/JCI8119 Bodzioch, 1999, The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease, Nat. Genet., 22, 347, 10.1038/11914 Wong, 2006, SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR, Biochem. J., 400, 485, 10.1042/BJ20060914 Zeng, 2004, Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: a novel role of SREBP in regulating cholesterol metabolism, J. Biol. Chem., 279, 48801, 10.1074/jbc.M407817200 Ito, 2015, LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling, elife, 4, e08009, 10.7554/eLife.08009 Chinetti, 2001, PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway, Nat. Med., 7, 53, 10.1038/83348 Hovingh, 2004, HDL deficiency and atherosclerosis: lessons from Tangier disease, J. Intern. Med., 255, 299, 10.1046/j.0954-6820.2003.01256.x Omiya, 2016, Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation, Am. J. Phys. Heart Circ. Phys., 311, H1485 Tatsi, 2013, The spectrum of HNF1A gene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations, Pediatr. Diabetes, 14, 526, 10.1111/pedi.12032 Knebel, 2016, Divergent phenotypes in siblings with identical novel mutations in the HNF-1alpha gene leading to maturity onset diabetes of the young type 3, BMC Med. Genet., 17, 36, 10.1186/s12881-016-0297-z Ovsyannikova, 2017 Kanthimathi, 2014, Glucokinase gene mutations (MODY 2) in Asian Indians, Diabetes Technol. Ther., 16, 180, 10.1089/dia.2013.0244 Brereton, 2014, Reversible changes in pancreatic islet structure and function produced by elevated blood glucose, Nat. Commun., 5, 4639, 10.1038/ncomms5639 Padilla, 2017, TRAF3IP2 mediates high glucose-induced endothelin-1 production as well as endothelin-1-induced inflammation in endothelial cells, Am. J. Phys. Heart Circ. Phys., 314, H52 Wang, 2017, Rosuvastatin improves myocardial hypertrophy after hemodynamic pressure overload via regulating the crosstalk of Nrf2/ARE and TGF-beta/Smads pathways in rat heart, Eur. J. Pharmacol., 820, 173, 10.1016/j.ejphar.2017.12.013 Chen, 2016, Smooth muscle FGF/TGFbeta cross talk regulates atherosclerosis progression, EMBO Mol. Med., 8, 712, 10.15252/emmm.201506181 Istas, 2017, Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease, Sci. Rep., 7, 5120, 10.1038/s41598-017-03434-0 Yu, 2016, DNMT1-PPARgamma pathway in macrophages regulates chronic inflammation and atherosclerosis development in mice, Sci. Rep., 6 Whitson, 2003, Neonatal mortality and leanness in mice lacking the ARID transcription factor Mrf-2, Biochem. Biophys. Res. Commun., 312, 997, 10.1016/j.bbrc.2003.11.026 Liu, 2017, Blood monocyte transcriptome and epigenome analyses reveal loci associated with human atherosclerosis, Nat. Commun., 8, 393, 10.1038/s41467-017-00517-4 Zhang, 2017, The mammalian target of rapamycin and DNA methyltransferase 1 axis mediates vascular endothelial dysfunction in response to disturbed flow, Sci. Rep., 7 Lv, 2016, Histone methyltransferase enhancer of Zeste homolog 2-mediated ABCA1 promoter DNA methylation contributes to the progression of atherosclerosis, PLoS One, 11, 10.1371/journal.pone.0157265 Cao, 2014, Histone deacetylase 9 represses cholesterol efflux and alternatively activated macrophages in atherosclerosis development, Arterioscler. Thromb. Vasc. Biol., 34, 1871, 10.1161/ATVBAHA.114.303393 Bekkering, 2016, Innate immune cell activation and epigenetic remodeling in symptomatic and asymptomatic atherosclerosis in humans in vivo, Atherosclerosis, 254, 228, 10.1016/j.atherosclerosis.2016.10.019 Choi, 2017, Carbon monoxide prevents TNF-alpha-induced eNOS downregulation by inhibiting NF-kappaB-responsive miR-155-5p biogenesis, Exp. Mol. Med., 49, 10.1038/emm.2017.193 Yang, 2015, MicroRNA-155 promotes atherosclerosis inflammation via targeting SOCS1, Cell. Physiol. Biochem., 36, 1371, 10.1159/000430303 Schober, 2014, MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1, Nat. Med., 20, 368, 10.1038/nm.3487 Qin, 2018, MicroRNA-142-3p induces atherosclerosis-associated endothelial cell apoptosis by directly targeting Rictor, Cell. Physiol. Biochem., 47, 1589, 10.1159/000490932 Ma, 2018, Associations of CXCL16, miR146a and miR146b in atherosclerotic apolipoprotein Eknockout mice, Mol. Med. Rep., 18, 2995 Liu, 2018, MicroRNA-217 attenuates intima-media complex thickness of ascending aorta measured by ultrasound bio-microscopy and inhibits inflammation and lipid metabolism in atherosclerotic models of ApoE(−/−) mice, Lipids Health Dis., 17, 170, 10.1186/s12944-018-0825-2 Pearson-Leary, 2017, Inflammation and vascular remodeling in the ventral hippocampus contributes to vulnerability to stress, Transl. Psychiatry, 7, 10.1038/tp.2017.122 Lin, 2017, Blockade of 146b-5p promotes inflammation in atherosclerosis-associated foam cell formation by targeting TRAF6, Exp. Ther. Med., 14, 5087 Ceolotto, 2017, miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways, Cardiovasc. Res., 113, 1627, 10.1093/cvr/cvx157 Burd, 2010, Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk, PLoS Genet., 6, 10.1371/journal.pgen.1001233 Song, 2017, Effect of circular ANRIL on the inflammatory response of vascular endothelial cells in a rat model of coronary atherosclerosis, Cell. Physiol. Biochem., 42, 1202, 10.1159/000478918 Conn, 2015, The RNA binding protein quaking regulates formation of circRNAs, Cell, 160, 1125, 10.1016/j.cell.2015.02.014 Liu, 2017, Silencing of circular RNA-ZNF609 ameliorates vascular endothelial dysfunction, Theranostics, 7, 2863, 10.7150/thno.19353 Zhou, 2015, RNA interference of myocyte enhancer factor 2A accelerates atherosclerosis in apolipoprotein E-deficient mice, PLoS One, 10 Suzuki, 2004, Myocyte enhancer factor 2 mediates vascular inflammation via the p38-dependent pathway, Circ. Res., 95, 42, 10.1161/01.RES.0000134631.75684.4A Aguilera-Aguirre, 2014, Innate inflammation induced by the 8-oxoguanine DNA glycosylase-1-KRAS-NF-kappaB pathway, J. Immunol., 193, 4643, 10.4049/jimmunol.1401625 Li, 2018, IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14 (Histone 3 Lysine 14), Arterioscler. Thromb. Vasc. Biol., 38, 599, 10.1161/ATVBAHA.117.310626 Ding, 2013, Oxidant stress in mitochondrial DNA damage, autophagy and inflammation in atherosclerosis, Sci. Rep., 3, 1077, 10.1038/srep01077 Wang, 2017, Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress, Sci. Rep., 8, 45917, 10.1038/srep45917 Sung, 2012, N-acetyl cysteine suppresses the foam cell formation that is induced by oxidized low density lipoprotein via regulation of gene expression, Mol. Biol. Rep., 39, 3001, 10.1007/s11033-011-1062-1 Luo, 2016, High uric acid activates the ROS-AMPK pathway, impairs CD68 expression and inhibits OxLDL-induced foam-cell formation in a human monocytic cell line, THP-1, Cell. Physiol. Biochem., 40, 538, 10.1159/000452567 Rajendrasozhan, 2008, SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease, Am. J. Respir. Crit. Care Med., 177, 861, 10.1164/rccm.200708-1269OC Stein, 2010, SIRT1 reduces endothelial activation without affecting vascular function in ApoE−/− mice, Aging, 2, 353, 10.18632/aging.100162 Pan, 2016, Resveratrol protects against TNF-alpha-induced injury in human umbilical endothelial cells through promoting sirtuin-1-induced repression of NF-KB and p38 MAPK, PLoS One, 11 Zeng, 2013, SIRT1 prevents atherosclerosis via liverXreceptor and NFkappaB signaling in a U937 cell model, Mol. Med. Rep., 8, 23, 10.3892/mmr.2013.1460 Li, 2007, SIRT1 deacetylates and positively regulates the nuclear receptor LXR, Mol. Cell, 28, 91, 10.1016/j.molcel.2007.07.032 Chen, 2017, Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway, J. Am. Heart Assoc., 6, 10.1161/JAHA.117.006347 Mukohda, 2017, Hypertension-causing mutation in peroxisome proliferator-activated receptor gamma impairs nuclear export of nuclear factor-kappaB p65 in vascular smooth muscle, Hypertension, 70, 174, 10.1161/HYPERTENSIONAHA.117.09276 Wen, 2017, PEDF improves atherosclerotic plaque stability by inhibiting macrophage inflammation response, Int. J. Cardiol., 235, 37, 10.1016/j.ijcard.2017.02.102 Hodis, 2009, High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial, Stroke, 40, 730, 10.1161/STROKEAHA.108.526798 Su, 2015, Niacin suppresses progression of atherosclerosis by inhibiting vascular inflammation and apoptosis of vascular smooth muscle cells, Med. Sci. Monit., 21, 4081, 10.12659/MSM.895547 Kim, 2015, Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA, Food Funct., 6, 3604, 10.1039/C5FO00738K Bowie, 2000, Vitamin C inhibits NF-kappa B activation by TNF via the activation of p38 mitogen-activated protein kinase, J. Immunol., 165, 7180, 10.4049/jimmunol.165.12.7180 Martinez-Moreno, 2017, High phosphate induces a pro-inflammatory response by vascular smooth muscle cells and modulation by vitamin D derivatives, Clin. Sci., 131, 1449, 10.1042/CS20160807 Lin, 2016, Coadministration of VDR and RXR agonists synergistically alleviates atherosclerosis through inhibition of oxidative stress: an in vivo and in vitro study, Atherosclerosis, 251, 273, 10.1016/j.atherosclerosis.2016.06.005 Chen, 2016, Vitamin D deficiency accelerates coronary artery disease progression in swine, Arterioscler. Thromb. Vasc. Biol., 36, 1651, 10.1161/ATVBAHA.116.307586 Huang, 2012, Vitamin E ameliorates ox-LDL-induced foam cells formation through modulating the activities of oxidative stress-induced NF-kappaB pathway, Mol. Cell. Biochem., 363, 11, 10.1007/s11010-011-1153-2 Maziere, 2004, Inhibition of insulin signaling by oxidized low density lipoprotein. Protective effect of the antioxidant vitamin E, Atherosclerosis, 175, 23, 10.1016/j.atherosclerosis.2004.02.006 Kumar, 2016, Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE(−/−) mice, Sci. Rep., 6 Li, 2017, Contrast-enhanced ultrasound imaging quantification of adventitial vasa vasorum in a rabbit model of varying degrees of atherosclerosis, Sci. Rep., 7, 7032, 10.1038/s41598-017-06127-w Stein, 2017, Efficacy of rosuvastatin in children with homozygous familial hypercholesterolemia and association with underlying genetic mutations, J. Am. Coll. Cardiol., 70, 1162, 10.1016/j.jacc.2017.06.058 Natarajan, 2017, Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting, Circulation, 135, 2091, 10.1161/CIRCULATIONAHA.116.024436 deGoma, 2016, Treatment gaps in adults with heterozygous familial hypercholesterolemia in the United States: data from the CASCADE-FH registry, Circ. Cardiovasc. Genet., 9, 240, 10.1161/CIRCGENETICS.116.001381 Vaessen, 2009, AAV gene therapy as a means to increase apolipoprotein (Apo) A-I and high-density lipoprotein-cholesterol levels: correction of murine ApoA-I deficiency, J. Gene Med., 11, 697, 10.1002/jgm.1344 Evans, 2011, Adeno-associated virus serotypes 7 and 8 outperform serotype 9 in expressing atheroprotective human apoE3 from mouse skeletal muscle, Metabolism, 60, 491, 10.1016/j.metabol.2010.04.015 Osman, 2009, Preliminary evaluation of a self-complementary AAV2/8 vector for hepatic gene transfer of human apoE3 to inhibit atherosclerotic lesion development in apoE-deficient mice, Atherosclerosis, 204, 121, 10.1016/j.atherosclerosis.2008.08.043 Lazaro, 2015, Targeting HSP90 ameliorates nephropathy and atherosclerosis through suppression of NF-kappaB and STAT signaling pathways in diabetic mice, Diabetes, 64, 3600, 10.2337/db14-1926 Du, 2016, DNA methylation in cystathionine-gamma-lyase (CSE) gene promoter induced by ox-LDL in macrophages and in apoE knockout mice, Biochem. Biophys. Res. Commun., 469, 776, 10.1016/j.bbrc.2015.11.132 Xue, 2017, CircLRP6 regulation of ZEB1 via miR-455 is involved in the epithelial-mesenchymal transition during arsenite-induced malignant transformation of human keratinocytes, Toxicol. Sci., 162, 450, 10.1093/toxsci/kfx269 Bostrom, 2016, Endothelial-mesenchymal transition in atherosclerotic lesion calcification, Atherosclerosis, 253, 124, 10.1016/j.atherosclerosis.2016.08.046