Abstract
Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis.
Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.
Keywords: Atherosclerosis, aging, vascular aging, endothelial dysfunction, inflammation, oxidative stress.
[http://dx.doi.org/10.1093/eurheartj/ehy468] [PMID: 30219877]
[http://dx.doi.org/10.1093/eurheartj/ehx239] [PMID: 29447349]
[http://dx.doi.org/10.1038/s41586-018-0457-8] [PMID: 30185958]
[http://dx.doi.org/10.2174/1381612822666160822124546] [PMID: 27549380]
[http://dx.doi.org/10.1093/ajcn/72.5.1307s] [PMID: 11063473]
[http://dx.doi.org/10.4070/kcj.2010.40.1.1] [PMID: 20111646]
[http://dx.doi.org/10.1001/jama.2012.70830] [PMID: 23268516]
[http://dx.doi.org/10.1161/CIR.0000000000000558] [PMID: 29386200]
[http://dx.doi.org/10.1093/eurheartj/ehw106] [PMID: 27222591]
[http://dx.doi.org/10.1016/j.jacc.2013.11.005] [PMID: 24239921]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.577460] [PMID: 16301361]
[http://dx.doi.org/10.1016/j.mad.2016.03.005] [PMID: 26993150]
[http://dx.doi.org/10.1161/CIR.0000000000000659] [PMID: 30700139]
[http://dx.doi.org/10.1016/j.jacc.2017.01.064] [PMID: 28408026]
[http://dx.doi.org/10.1093/eurheartj/ehv587] [PMID: 26543043]
[PMID: 1852778]
[http://dx.doi.org/10.1016/0735-1097(94)90305-0] [PMID: 8034885]
[http://dx.doi.org/10.1161/01.CIR.0000048892.83521.58] [PMID: 12515756]
[http://dx.doi.org/10.1161/01.RES.0000269183.13937.e8] [PMID: 17478731]
[http://dx.doi.org/10.1002/cphy.c160029] [PMID: 28333382]
[http://dx.doi.org/10.1016/j.vph.2017.10.003] [PMID: 29051088]
[http://dx.doi.org/10.1007/s11883-017-0644-3] [PMID: 28185154]
[http://dx.doi.org/10.3390/ijms17121967] [PMID: 27898011]
[http://dx.doi.org/10.1016/j.ijcard.2018.01.008] [PMID: 29317141]
[http://dx.doi.org/10.1111/eci.12692] [PMID: 27759884]
[http://dx.doi.org/10.1016/j.ijcard.2018.03.081] [PMID: 29754909]
[http://dx.doi.org/10.1016/j.vph.2017.12.066] [PMID: 29305337]
[http://dx.doi.org/10.1016/j.ijcard.2018.07.112] [PMID: 30075966]
[http://dx.doi.org/10.1111/eci.12888] [PMID: 29327345]
[http://dx.doi.org/10.1113/jphysiol.2007.147686] [PMID: 18063659]
[http://dx.doi.org/10.1084/jem.192.12.1731] [PMID: 11120770]
[http://dx.doi.org/10.1097/00005344-198906146-00014] [PMID: 2478827]
[http://dx.doi.org/10.1111/j.1474-9726.2006.00232.x] [PMID: 16930126]
[http://dx.doi.org/10.1152/ajpheart.00689.2008] [PMID: 19465546]
[http://dx.doi.org/10.2174/13816128113196660746] [PMID: 24180388]
[http://dx.doi.org/10.2174/13816128113196660748] [PMID: 24180381]
[http://dx.doi.org/10.1161/CIRCRESAHA.107.162701] [PMID: 17901365]
[http://dx.doi.org/10.1152/japplphysiol.90627.2008] [PMID: 18719233]
[http://dx.doi.org/10.1155/2014/615312] [PMID: 25143940]
[http://dx.doi.org/10.1093/eurheartj/ehv679] [PMID: 26690751]
[http://dx.doi.org/10.1093/eurheartj/ehy607] [PMID: 30295766]
[http://dx.doi.org/10.1016/j.jacc.2017.05.035] [PMID: 28683969]
[http://dx.doi.org/10.1016/j.molcel.2007.04.021] [PMID: 17560373]
[http://dx.doi.org/10.1128/MCB.25.6.2320-2330.2005] [PMID: 15743827]
[http://dx.doi.org/10.1007/s11883-017-0646-1] [PMID: 28194569]
[http://dx.doi.org/10.1016/j.jacc.2017.09.028] [PMID: 29073957]
[http://dx.doi.org/10.1089/ars.2012.4604] [PMID: 22443458]
[http://dx.doi.org/10.1016/j.bcp.2006.04.011] [PMID: 16723122]
[http://dx.doi.org/10.1038/cr.2010.178] [PMID: 21187859]
[http://dx.doi.org/10.1038/sj.bjp.0703632] [PMID: 11030731]
[http://dx.doi.org/10.1152/physiolgenomics.00136.2007] [PMID: 18056786]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.088294] [PMID: 17576858]
[http://dx.doi.org/10.3390/ijms17020193] [PMID: 26840309]
[http://dx.doi.org/10.3389/fphys.2018.01744] [PMID: 30568599]
[http://dx.doi.org/10.1515/REVNEURO.2009.20.1.23] [PMID: 19526732]
[PMID: 1562050]
[http://dx.doi.org/10.1097/MNH.0b013e3283361c0b] [PMID: 20040868]
[http://dx.doi.org/10.3389/fgene.2017.00126] [PMID: 29085385]
[http://dx.doi.org/10.1161/CIRCRESAHA.115.307722] [PMID: 26846637]
[http://dx.doi.org/10.3389/fgene.2015.00112] [PMID: 25926844]
[http://dx.doi.org/10.1159/000331278] [PMID: 22105095]
[PMID: 3456347]
[http://dx.doi.org/10.1097/00004872-200301000-00002] [PMID: 12544424]
[http://dx.doi.org/10.1161/01.ATV.11.5.1223] [PMID: 1911708]
[http://dx.doi.org/10.1161/01.HYP.33.1.116] [PMID: 9931091]
[http://dx.doi.org/10.1016/j.amjhyper.2004.11.011] [PMID: 15831360]
[http://dx.doi.org/10.1093/cvr/cvw061] [PMID: 27009176]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03617] [PMID: 25368028]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.090464] [PMID: 19948990]
[http://dx.doi.org/10.1016/j.hfc.2011.08.011] [PMID: 22108734]
[http://dx.doi.org/10.1016/j.mad.2015.11.001] [PMID: 26590322]
[http://dx.doi.org/10.1016/j.amjmed.2008.10.013] [PMID: 19110086]
[http://dx.doi.org/10.1016/0021-9150(94)90036-1] [PMID: 7980706]
[http://dx.doi.org/10.1016/j.carpath.2005.03.002] [PMID: 15914297]
[http://dx.doi.org/10.1161/STROKEAHA.110.587006] [PMID: 20814007]
[http://dx.doi.org/10.1161/STROKEAHA.110.607382] [PMID: 21737811]
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.08.042] [PMID: 25240113]
[http://dx.doi.org/10.1161/STROKEAHA.115.010558] [PMID: 26451032]
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306247] [PMID: 26892971]
[http://dx.doi.org/10.1160/TH16-08-0593] [PMID: 27683760]
[http://dx.doi.org/10.1161/01.CIR.0000034392.34211.FC] [PMID: 12370230]
[http://dx.doi.org/10.4244/EIJV8I8A142] [PMID: 23253546]
[http://dx.doi.org/10.1016/j.ijcard.2011.01.041] [PMID: 21316114]
[http://dx.doi.org/10.1148/radiol.11101652] [PMID: 21734157]
[http://dx.doi.org/10.1093/eurheartj/ehr227] [PMID: 21821844]
[http://dx.doi.org/10.1118/1.4754302] [PMID: 23039660]
[http://dx.doi.org/10.1016/j.amjcard.2014.08.001] [PMID: 25245415]
[http://dx.doi.org/10.1161/CIRCRESAHA.111.261388] [PMID: 22773427]
[PMID: 3354639]
[http://dx.doi.org/10.3389/fimmu.2018.00586] [PMID: 29686666]
[http://dx.doi.org/10.1160/TH17-09-0630] [PMID: 29304522]
[PMID: 15198963]
[http://dx.doi.org/10.1161/01.RES.73.2.223] [PMID: 8101140]
[http://dx.doi.org/10.1016/j.cardiores.2003.09.018] [PMID: 14659813]
[http://dx.doi.org/10.1172/JCI117917] [PMID: 7738191]
[http://dx.doi.org/10.1161/01.RES.0000233315.38086.bc] [PMID: 16794190]
[http://dx.doi.org/10.1161/01.RES.82.6.704] [PMID: 9546379]
[http://dx.doi.org/10.1161/hh0901.090305] [PMID: 11348998]
[http://dx.doi.org/10.1093/eurheartj/ehw073] [PMID: 26941203]
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.07.118] [PMID: 21855069]
[http://dx.doi.org/10.1016/S0008-6363(98)00311-3] [PMID: 10341847]
[http://dx.doi.org/10.1073/pnas.92.20.9363] [PMID: 7568133]
[http://dx.doi.org/10.1146/annurev-pathol-121808-102144] [PMID: 20078217]
[http://dx.doi.org/10.1161/01.CIR.0000013836.85741.17] [PMID: 11927518]
[http://dx.doi.org/10.1016/j.drudis.2017.01.004] [PMID: 28111332]
[http://dx.doi.org/10.1016/S0140-6736(01)05633-1] [PMID: 11513915]
[http://dx.doi.org/10.1161/ATVBAHA.111.237271] [PMID: 22199369]
[http://dx.doi.org/10.1139/Y08-082] [PMID: 19011671]
[http://dx.doi.org/10.1016/j.dnarep.2005.06.003] [PMID: 16006199]
[http://dx.doi.org/10.1016/j.ijcard.2017.09.188] [PMID: 28988828]
[http://dx.doi.org/10.1038/46311] [PMID: 10580504]
[http://dx.doi.org/10.1126/science.1215135] [PMID: 22461615]
[http://dx.doi.org/10.1016/j.cell.2007.05.038] [PMID: 17662940]
[http://dx.doi.org/10.1016/j.cmet.2007.12.010] [PMID: 18249171]
[http://dx.doi.org/10.1016/j.cmet.2013.07.013] [PMID: 24011076]
[http://dx.doi.org/10.1016/j.cell.2005.11.044] [PMID: 16439206]
[http://dx.doi.org/10.1038/nature10815] [PMID: 22367546]
[http://dx.doi.org/10.1038/36285] [PMID: 9363890]
[http://dx.doi.org/10.1126/science.1112766] [PMID: 16123266]
[http://dx.doi.org/10.1161/ATVBAHA.107.156059] [PMID: 18162611]
[http://dx.doi.org/10.2174/157016112803520747] [PMID: 23259557]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02129] [PMID: 24842918]
[http://dx.doi.org/10.1161/01.CIR.0000147731.24444.4D] [PMID: 15505103]
[http://dx.doi.org/10.1016/j.ijcard.2014.06.025] [PMID: 25012499]
[http://dx.doi.org/10.1093/eurheartj/ehv140] [PMID: 25904764]
[http://dx.doi.org/10.1093/eurheartj/ehs331] [PMID: 23008506]
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.10.035] [PMID: 22100252]
[http://dx.doi.org/10.1161/ATVBAHA.111.229260] [PMID: 21817106]
[http://dx.doi.org/10.1371/journal.pone.0107787] [PMID: 25247687]
[http://dx.doi.org/10.1073/pnas.0336359100] [PMID: 12571362]
[http://dx.doi.org/10.1080/10623320802487791] [PMID: 19065319]
[http://dx.doi.org/10.1038/s42003-018-0108-5] [PMID: 30271984]
[http://dx.doi.org/10.1155/2015/250310] [PMID: 25945149]
[http://dx.doi.org/10.1016/j.bbadis.2014.08.012] [PMID: 25193033]
[http://dx.doi.org/10.1038/268252a0] [PMID: 196205]
[http://dx.doi.org/10.1152/ajpheart.00080.2013] [PMID: 23624627]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.001212] [PMID: 23536361]
[http://dx.doi.org/10.1124/jpet.116.232538] [PMID: 26941173]
[http://dx.doi.org/10.1074/jbc.M314238200] [PMID: 15262973]
[http://dx.doi.org/10.1038/nature11861] [PMID: 23325216]
[http://dx.doi.org/10.1172/JCI43008] [PMID: 20644257]
[http://dx.doi.org/10.1371/journal.pone.0054221] [PMID: 23342106]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.977066] [PMID: 21357822]
[http://dx.doi.org/10.1161/01.CIR.0000057979.36322.88] [PMID: 12668503]
[http://dx.doi.org/10.1161/01.CIR.0000130641.08705.45] [PMID: 15184287]
[http://dx.doi.org/10.1016/j.ajpath.2013.02.012] [PMID: 23567640]
[http://dx.doi.org/10.1161/CIRCRESAHA.111.249532] [PMID: 21737790]
[http://dx.doi.org/10.1016/j.jacc.2009.08.031] [PMID: 20082935]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.078212] [PMID: 22294621]
[http://dx.doi.org/10.3389/fphys.2012.00005] [PMID: 22291661]
[http://dx.doi.org/10.1093/eurheartj/ehp259] [PMID: 19567381]
[http://dx.doi.org/10.1113/jphysiol.2003.040691] [PMID: 12813156]
[http://dx.doi.org/10.1073/pnas.252625599] [PMID: 12444247]
[http://dx.doi.org/10.1016/j.cmet.2007.01.008] [PMID: 17276357]
[http://dx.doi.org/10.1073/pnas.0705070104] [PMID: 17609368]
[http://dx.doi.org/10.1016/j.molcel.2008.03.003] [PMID: 18439900]
[http://dx.doi.org/10.1038/nature06322] [PMID: 18046414]
[http://dx.doi.org/10.1038/onc.2008.120] [PMID: 18427548]
[http://dx.doi.org/10.1038/sj.onc.1208901] [PMID: 16007120]
[http://dx.doi.org/10.1074/jbc.M408143200] [PMID: 15563473]
[http://dx.doi.org/10.1042/BJ20061436] [PMID: 17253961]
[http://dx.doi.org/10.1093/cvr/cvn224] [PMID: 18689793]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000826]
[http://dx.doi.org/10.1038/nrm3293] [PMID: 22395773]
[http://dx.doi.org/10.1038/nrc2962] [PMID: 21102633]
[http://dx.doi.org/10.1093/gerona/62.9.960] [PMID: 17895433]
[http://dx.doi.org/10.1371/journal.pone.0058636] [PMID: 23505545]
[http://dx.doi.org/10.1152/ajpheart.00871.2013] [PMID: 24973384]
[http://dx.doi.org/10.3892/mmr.2014.2648] [PMID: 25323555]
[PMID: 30165439]
[http://dx.doi.org/10.3390/ijms14023834] [PMID: 23434668]
[http://dx.doi.org/10.1093/eurheartj/ehu095] [PMID: 24603306]
[http://dx.doi.org/10.18632/aging.101068] [PMID: 27744418]
[http://dx.doi.org/10.2337/db09-1187] [PMID: 20068143]
[http://dx.doi.org/10.1016/j.cmet.2008.08.014] [PMID: 18840364]
[http://dx.doi.org/10.1111/j.1474-9726.2007.00335.x] [PMID: 17877786]
[http://dx.doi.org/10.1111/jcmm.12395] [PMID: 25210848]
[http://dx.doi.org/10.1016/S0531-5565(03)00209-2] [PMID: 14580859]
[http://dx.doi.org/10.1007/s11357-013-9559-2] [PMID: 23839864]
[http://dx.doi.org/10.1371/journal.pone.0115616] [PMID: 25541994]
[http://dx.doi.org/10.1016/j.ijcard.2017.12.060] [PMID: 29622432]
[http://dx.doi.org/10.1016/j.bbamcr.2011.03.001] [PMID: 21396404]
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.05.002] [PMID: 23665396]
[http://dx.doi.org/10.1042/BJ20140213] [PMID: 25162939]
[http://dx.doi.org/10.1007/s00395-013-0399-0] [PMID: 24370889]
[http://dx.doi.org/10.1007/s11010-012-1236-8] [PMID: 22286818]
[http://dx.doi.org/10.1038/cr.2016.8] [PMID: 26780861]
[PMID: 27519885]
[http://dx.doi.org/10.1371/journal.pone.0176371] [PMID: 28448551]
[http://dx.doi.org/10.1016/j.tem.2016.10.002] [PMID: 27836583]
[http://dx.doi.org/10.18632/aging.100975] [PMID: 27249230]
[http://dx.doi.org/10.2337/db14-1149] [PMID: 25325735]
[http://dx.doi.org/10.1111/ajt.13415] [PMID: 26280899]
[http://dx.doi.org/10.1210/er.2013-1079] [PMID: 25695404]
[http://dx.doi.org/10.1016/j.febslet.2009.09.009] [PMID: 19737556]
[PMID: 26347327]
[http://dx.doi.org/10.1016/j.bbagen.2009.02.005] [PMID: 19230844]
[http://dx.doi.org/10.1523/JNEUROSCI.5791-12.2015] [PMID: 25673831]
[http://dx.doi.org/10.4330/wjc.v6.i12.1262] [PMID: 25548616]
[http://dx.doi.org/10.1074/jbc.M509039200] [PMID: 16186101]
[http://dx.doi.org/10.1111/j.1474-9726.2012.00796.x] [PMID: 22260450]
[http://dx.doi.org/10.1371/journal.pone.0082968] [PMID: 24340070]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.07709] [PMID: 27620389]
[http://dx.doi.org/10.1007/s11682-016-9598-2] [PMID: 27714549]
[http://dx.doi.org/10.1042/CS20171242] [PMID: 28963437]
[PMID: 30879355]
[http://dx.doi.org/10.1093/eurheartj/ehx566] [PMID: 29069377]
[http://dx.doi.org/10.1016/S0195-668X(02)00419-0] [PMID: 12590901]
[http://dx.doi.org/10.2174/0929867324666170303123734] [PMID: 28260498]
[http://dx.doi.org/10.1161/01.CIR.96.12.4211] [PMID: 9416884]
[http://dx.doi.org/10.7326/0003-4819-134-10-200105150-00007] [PMID: 11352694]
[http://dx.doi.org/10.1016/S0140-6736(02)09327-3] [PMID: 12114036]
[http://dx.doi.org/10.1016/j.jacc.2013.07.069] [PMID: 23954343]
[http://dx.doi.org/10.1016/j.jacc.2007.06.063] [PMID: 18174034]
[http://dx.doi.org/10.1016/S0140-6736(18)31942-1] [PMID: 30712900]
[http://dx.doi.org/10.1111/bcp.12687] [PMID: 26032930]
[http://dx.doi.org/10.1093/eurheartj/ehv304] [PMID: 26163482]
[http://dx.doi.org/10.1016/S0140-6736(09)60503-1] [PMID: 19482214]
[http://dx.doi.org/10.1001/jama.2014.15690] [PMID: 25401325]