Vascular Endothelial Cell Senescence and Vascular Diseases
MENG Mei, XIONG Xing-Dong*
1) Institute of Aging Research, Guangdong Medical College, Dongguan 523808, Guangdong, China;
2) Institute of Biochemistry & Molecular Biology, Guangdong Medical College, Zhanjiang 524023, Guangdong, China;
3) Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan 523808, Guangdong, China
Abstract：Cell senescence is manifested as irreversible proliferation arrest in response to various types of stress, which is accompanied by specific changes in cell function, morphology and gene expression. Growing evidence demonstrated that most molecules involved in cellular senescence of endothelial cells were able to influence vascular physiological functions and contributed age-related vascular diseases. In this review, we summarized the recent progress on the endothelial senescence-related signaling pathways, and the effects of endothelial senescence on the vascular functions and diseases of atherosclerosis, hypertension and the vascular complications in diabetes mellitus. It may help to understand the molecular mechanisms of endothelial cell senescence, particularly on how vascular endothelial cells become senescent and how the senescence causes vascular dysfunction and contributes to vascular diseases.
Kovacic JC, Moreno P, Hachinski V, et al.Cellular senescence,vascular disease,and aging: Part 1 of a 2-part review[J].Circulation, 2011, 123(15):1650-1660
[3]
Reaper PM, di Fagagna Fd, Jackson SP.Activation of the DNA damage response by telomere attrition: a passage to cellular senescence[J].Cell Cycle, 2004, 3(5):543-546
[8]
Tait IS, Li Y, Lu J.Effects of PTEN on the longevity of cultured human umbilical vein endothelial cells: the role of antioxidants[J].Int J Mol Med, 2015, 35(1):277-284
[10]
Ota H, Akishita M, Eto M, et al.Sirt1 modulates premature senescence-like phenotype in human endothelial cells[J].J Mol Cell Cardiol, 2007, 43(5):571-579
[1]
Vigen R, Maddox TM, Allen LA.Aging of the United States population: impact on heart failure[J].Curr Heart Fail Rep, 2012, 9(4):369-374
[5]
Chen Q, Ames BN.Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells[J].Proc Natl Acad Sci USA, 1994, 91(10):4130-4134
[14]
Song Z, Liu Y, Hao B, et al.Ginsenoside Rb1 prevents H2O2-induced HUVEC senescence by stimulating sirtuin-1 pathway[J].PLoS One, 2014, 9(11):e112699-
[39]
Che P, Liu J, Shan Z, et al.miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation[J].Aging Cell, 2014, 13(5):926-934
[6]
Balin AK, Fisher AJ, Anzelone M, et al.Effects of establishing cell cultures and cell culture conditions on the proliferative life span of human fibroblasts isolated from different tissues and donors of different ages[J].Exp Cell Res, 2002, 274(2):275-287
[11]
Zu Y, Liu L, Lee MY, et al.SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells[J].Circ Res, 2010, 106(8):1384-1393
[13]
Rippe C, Lesniewski L, Connell M, et al.Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress[J].Aging Cell, 2010, 9(3):304-312
[16]
Cardus A, Uryga AK, Walters G, et al.SIRT6 protects human endothelial cells from DNA damage,telomere dysfunction,and senescence[J].Cardiovasc Res, 2013, 97(3):571-579
[19]
Ichijo H, Nishida E, Irie K, et al.Induction of apoptosis by ASK1,a mammalian MAPKKK that activates SAPKJNK and p38 signaling pathways[J].Science, 1997, 275(5296):90-94
Van Balkom BW, de Jong OG, et al.Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells[J].Blood, 2013, 121(19):3997-
[24]
Shi Y, Luscher TF, Camici GG.Dual role of endothelial nitric oxide synthase in oxidized LDL-induced,p66Shc-mediated oxidative stress in cultured human endothelial cells[J].PLoS One, 2014, 9(9):e107787-
Cheng HS, Njock MS, Khyzha N, et al.Noncoding RNAs regulate NF-kappaB signaling to modulate blood vessel inflammation [J]. Front Genet, 2014, 5: 422
[4]
Bringold F, Serrano M.Tumor suppressors and oncogenes in cellular senescence[J].Exp Gerontol, 2000, 35(3):317-329
[7]
Miyauchi H, Minamino T, Tateno K, et al.Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53p21-dependent pathway[J].EMBO J, 2004, 23(1):212-220
[12]
Menghini R, Casagrande V, Cardellini M, et al.MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1[J].Circulation, 2009, 120(15):1524-1532
[15]
Botden IP, Oeseburg H, Durik M, et al.Red wine extract protects against oxidative-stress-induced endothelial senescence[J].Clin Sci (Lond), 2012, 123(8):499-507
[20]
Adelibieke Y, Shimizu H, Muteliefu G, et al.Indoxyl sulfate induces endothelial cell senescence by increasing reactive oxygen species production and p53 activity[J].J Ren Nutr, 2012, 22(1):86-89
[23]
Coleman PR, Hahn CN, Grimshaw M, et al.Stress-induced premature senescence mediated by a novel gene,SENEX,results in an anti-inflammatory phenotype in endothelial cells[J].Blood, 2010, 116(19):4016-
[27]
Ge D, Han L, Huang S, et al.Identification of a novel MTOR activator and discovery of a competing endogenous RNA regulating autophagy in vascular endothelial cells[J].Autophagy, 2014, 10(6):957-971
[28]
Peng N, Meng N, Wang S, et al.An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E(-)/(-) mice [J]. Sci Rep, 2014, 4: 5519
[31]
Rajapakse AG, Yepuri G, Carvas JM, et al.Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol[J].PLoS One, 2011, 6(4):e19237-
[33]
Voghel G, Thorin-Trescases N, Mamarbachi AM, et al.Endogenous oxidative stress prevents telomerase- dependent immortalization of human endothelial cells[J].Mech Ageing Dev, 2010, 131(5):354-363
[37]
Guarani V, Deflorian G, Franco CA, et al.Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase[J].Nature, 2011, 473(7346):234-238
[40]
Schleicher M, Shepherd BR, Suarez Y, et al.Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence[J].J Cell Biol, 2008, 180(1):101-112
[46]
Schalkwijk CG, Stehouwer CD.Vascular complications in diabetes mellitus: the role of endothelial dysfunction[J].Clin Sci (Lond), 2005, 109(2):143-159
[49]
Orimo M, Minamino T, Miyauchi H, et al.Protective role of SIRT1 in diabetic vascular dysfunction[J].Arterioscler Thromb Vasc Biol, 2009, 29(6):889-894
[2]
Minamino T, Miyauchi H, Yoshida T, et al.The role of vascular cell senescence in atherosclerosis: antisenescence as a novel therapeutic strategy for vascular aging[J].Curr Vasc Pharmacol, 2004, 2(2):141-
[9]
Potente M, Ghaeni L, Baldessari D, et al.SIRT1 controls endothelial angiogenic functions during vascular growth[J].Genes Dev, 2007, 21(20):2644-2658
[17]
Liu R, Liu H, Ha Y, et al.Oxidative stress induces endothelial cell senescence via downregulation of Sirt6 [J]. Biomed Res Int, 2014, 2014: 902842
[18]
Zhan H, Suzuki T, Aizawa K, et al.Ataxia telangiectasia mutated (ATM)-mediated DNA damage response in oxidative stress-induced vascular endothelial cell senescence[J].J Biol Chem, 2010, 285(38):29662-
[25]
Yang Z, Ming XF.Arginase: the emerging therapeutic target for vascular oxidative stress and inflammation [J]. Front Immunol, 2013, 4: 149
[26]
Xiong Y, Yepuri G, Forbiteh M, et al.ARG2 impairs endothelial autophagy through regulation of MTOR and PRKAAAMPK signaling in advanced atherosclerosis[J].Autophagy, 2014, 10(12):2223-2238
[34]
Ito TK, Yokoyama M, Yoshida Y, et al.A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis[J].PLoS One, 2014, 9(7):e102186-
[43]
Zhang L, Connelly JJ, Peppel K, et al.Aging-related atherosclerosis is exacerbated by arterial expression of tumor necrosis factor receptor-1: evidence from mouse models and human association studies[J].Hum Mol Genet, 2010, 19(14):2754-2766
[44]
Zhang L, Peppel K, Sivashanmugam P, et al.Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis[J].Arterioscler Thromb Vasc Biol, 2007, 27(5):1087-1094
[52]
Zhou Z, Peng J, Wang CJ, et al.Accelerated senescence of endothelial progenitor cells in hypertension is related to the reduction of calcitonin gene-related peptide[J].J Hypertens, 2010, 28(5):931-939
[53]
Kaess BM, Rong J, Larson MG, et al.Aortic stiffness,blood pressure progression,and incident hypertension[J].JAMA, 2012, 308(9):875-881
[29]
Wang W, Liu X, Zhang Y, et al.Both senescence and apoptosis induced by deprivation of growth factors were inhibited by a novel butyrolactone derivative through depressing integrin beta4 in vascular endothelial cells[J].Endothelium, 2007, 14(6):325-332
[38]
Zheng Y, Xu Z.MicroRNA-22 induces endothelial progenitor cell senescence by targeting AKT3[J].Cell Physiol Biochem, 2014, 34(5):1547-1555
[47]
Chen J, Brodsky SV, Goligorsky DM, et al.Glycated collagen I induces premature senescence-like phenotypic changes in endothelial cells[J].Circ Res, 2002, 90(12):1290-1298
[30]
Chen F, Chen B, Xiao FQ, et al.Autophagy protects against senescence and apoptosis via the RAS- mitochondria in high-glucose-induced endothelial cells[J].Cell Physiol Biochem, 2014, 33(4):1058-1074
Huynh J, Nishimura N, Rana K, et al.Age-related intimal stiffening enhances endothelial permeability and leukocyte transmigration[J].Sci Transl Med, 2011, 3(112):112-r
[48]
Brodsky SV, Gealekman O, Chen J, et al.Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen[J].Circ Res, 2004, 94(3):377-384
[42]
Minamino T, Miyauchi H, Yoshida T, et al.Endothelial cell senescence in human atherosclerosis: role of telomeres in endothelial dysfunction[J].J Cardiol, 2003, 41(1):39-40
[50]
Yuan Q, Hu CP, Gong ZC, et al.Accelerated onset of senescence of endothelial progenitor cells in patients with type 2 diabetes mellitus: role of dimethylarginine dimethylaminohydrolase 2 and asymmetric dimethylarginine[J].Biochem Biophys Res Commun, 2015, 458(4):869-876
[51]
Chang J, Li Y, Huang Y, et al.Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAP kinasep16INK4A signaling pathway[J].Diabetes, 2010, 59(11):2949-2959
