Abstract
The endothelium consists of a monolayer of Endothelial Cells (ECs) which form the inner cellular lining of veins, arteries, capillaries and lymphatic vessels. ECs interact with the blood and lymph. The endothelium fulfils functions such as vasodilatation, regulation of adhesion, infiltration of leukocytes, inhibition of platelet adhesion, vessel remodeling and lipoprotein metabolism. ECs synthesize and release compounds such as Nitric Oxide (NO), metabolites of arachidonic acid, Reactive Oxygen Species (ROS) and enzymes that degrade the extracellular matrix. Endothelial dysfunction represents a phenotype prone to atherogenesis and may be used as a marker of atherosclerotic risk. Such dysfunction includes impaired synthesis and availability of NO and an imbalance in the relative contribution of endothelialderived relaxing factors and contracting factors such as endothelin-1 and angiotensin. This dysfunction appears before the earliest anatomic evidence of atherosclerosis and could be an important initial step in further development of atherosclerosis. Endothelial dysfunction was historically treated with vitamin C supplementation and L-arginine supplementation. Short term improvement of the expression of adhesion molecule and endothelial function during antioxidant therapy has been observed. Statins are used in the treatment of hyperlipidaemia, a risk factor for cardiovascular disease. Future studies should focus on identifying the mechanisms involved in the beneficial effects of statins on the endothelium. This may help develop drugs specifically aimed at endothelial dysfunction.
Keywords: Hyperlipidaemia, endothelium, endothelial dysfunction, statins, cardiovascular disease, atherosclerosis.
[PMID: 16999215]
[http://dx.doi.org/10.1016/S0046-8177(87)80005-9] [PMID: 3546072]
[http://dx.doi.org/10.4199/C00031ED1V01Y201105ISP019] [PMID: 21850763]
[http://dx.doi.org/10.1016/S0008-6363(99)00150-9] [PMID: 10536661]
[http://dx.doi.org/10.1161/01.CIR.87.3.705] [PMID: 8443891]
[http://dx.doi.org/10.1016/S0033-0620(98)80008-X] [PMID: 9790413]
[http://dx.doi.org/10.1038/nature05487] [PMID: 17167476]
[http://dx.doi.org/10.1042/CS20070115] [PMID: 18184112]
[http://dx.doi.org/10.1161/CIR.0000000000000485] [PMID: 28122885]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012477] [PMID: 25623155]
[http://dx.doi.org/10.1161/01.CIR.31.3.321] [PMID: 14262568]
[http://dx.doi.org/10.1177/1538574416628654] [PMID: 26983667]
[http://dx.doi.org/10.1161/01.CIR.101.15.1780] [PMID: 10769277]
[http://dx.doi.org/10.2337/dc09-S330] [PMID: 19875572]
[http://dx.doi.org/10.2215/CJN.04291007] [PMID: 18256374]
[http://dx.doi.org/10.1161/01.CIR.101.11.1261] [PMID: 10725285]
[http://dx.doi.org/10.1172/JCI115987] [PMID: 1401062]
[http://dx.doi.org/10.1038/344160a0] [PMID: 2106627]
[http://dx.doi.org/10.1097/CRD.0b013e31829dea90] [PMID: 23873211]
[http://dx.doi.org/10.1161/01.CIR.95.12.2617] [PMID: 9193429]
[http://dx.doi.org/10.1016/S0735-1097(97)00536-6] [PMID: 9502634]
[http://dx.doi.org/10.1016/S0735-1097(96)00394-4] [PMID: 8962569]
[http://dx.doi.org/10.1016/S0735-1097(97)00279-9] [PMID: 9350919]
[http://dx.doi.org/10.1172/JCI114688] [PMID: 2195060]
[PMID: 25001649]
[http://dx.doi.org/10.1096/fj.03-0301fje] [PMID: 14597560]
[http://dx.doi.org/10.1161/CIRCRESAHA.118.313237] [PMID: 30355249]
[http://dx.doi.org/10.1186/s12872-015-0124-z] [PMID: 26481314]
[http://dx.doi.org/10.2174/1389557515666150226114031] [PMID: 25723463 ]
[http://dx.doi.org/10.1007/s00281-011-0285-5] [PMID: 21845431]
[http://dx.doi.org/10.1161/01.RES.0000255691.76142.4a] [PMID: 17272818]
[http://dx.doi.org/10.1007/3-540-36028-X_6] [PMID: 16999228]
[http://dx.doi.org/10.1152/physrev.00016.2011] [PMID: 23303912]
[http://dx.doi.org/10.1161/01.HYP.0000209952.30603.e9] [PMID: 16520404 ]
[http://dx.doi.org/10.1053/beha.1999.0028] [PMID: 10856973]
[http://dx.doi.org/10.1055/s-2000-13205] [PMID: 11129405]
[http://dx.doi.org/10.1038/346074a0] [PMID: 2366866]
[http://dx.doi.org/10.1182/blood-2011-03-341107] [PMID: 21803853]
[http://dx.doi.org/10.1074/jbc.M708985200] [PMID: 18424440]
[http://dx.doi.org/10.1053/beha.1999.0030] [PMID: 10856975]
[http://dx.doi.org/10.1111/j.1365-2516.2008.01848.x] [PMID: 18786007]
[http://dx.doi.org/10.1160/th15-08-0620] [PMID: 26632869]
[http://dx.doi.org/10.1227/01.NEU.0000363148.49779.68] [PMID: 20023547]
[http://dx.doi.org/10.1016/j.jconrel.2015.09.055] [PMID: 26435455]
[http://dx.doi.org/10.1016/j.gendis.2016.02.003] [PMID: 30258888]
[http://dx.doi.org/10.1016/j.gep.2016.05.001] [PMID: 27221232]
[http://dx.doi.org/10.1152/ajplegacy.1959.196.2.381] [PMID: 13627187]
[http://dx.doi.org/10.1056/NEJM199007053230105] [PMID: 2355955]
[http://dx.doi.org/10.1161/01.ATV.0000051384.43104.FC] [PMID: 12588755]
[http://dx.doi.org/10.1097/00004872-200502000-00001] [PMID: 15662207]
[PMID: 3010744]
[http://dx.doi.org/10.4149/gpb_2010_04_319] [PMID: 21156995]
[http://dx.doi.org/10.1113/jphysiol.1983.sp014519] [PMID: 6875896]
[http://dx.doi.org/10.1038/308645a0] [PMID: 6424031]
[http://dx.doi.org/10.1161/01.CIR.91.9.2345] [PMID: 7729020]
[http://dx.doi.org/10.1152/ajpcell.1994.267.5.C1405] [PMID: 7977701]
[http://dx.doi.org/10.1021/tx00030a017] [PMID: 1336991]
[http://dx.doi.org/10.1161/01.CIR.0000089190.95415.9F] [PMID: 14568885]
[http://dx.doi.org/10.1161/hh1201.092042] [PMID: 11420306]
[PMID: 19644578]
[http://dx.doi.org/10.1002/jcp.26791] [PMID: 29932219]
[http://dx.doi.org/10.1161/01.CIR.0000029802.88087.5E] [PMID: 12186793]
[http://dx.doi.org/10.1373/49.8.1258] [PMID: 12881440]
[http://dx.doi.org/10.1186/1471-2121-9-47] [PMID: 18764931]
[http://dx.doi.org/10.1046/j.1523-1755.2001.0590041466.x] [PMID: 11260409]
[http://dx.doi.org/10.1097/01.ASN.0000132474.50966.DA] [PMID: 15284284 ]
[http://dx.doi.org/10.1161/hy09t1.094005] [PMID: 11566940]
[http://dx.doi.org/10.1007/s00125-010-1684-1] [PMID: 20361178]
[http://dx.doi.org/10.1096/fj.04-2263com] [PMID: 15522914]
[http://dx.doi.org/10.1172/JCI119636] [PMID: 9276741]
[http://dx.doi.org/10.1161/01.CIR.96.10.3287] [PMID: 9396418]
[http://dx.doi.org/10.1074/jbc.274.45.32512] [PMID: 10542298 ]
[http://dx.doi.org/10.1016/j.hfc.2012.06.012] [PMID: 22999242]
[http://dx.doi.org/10.1161/01.ATV.0000083297.47245.DA] [PMID: 12829522]
[http://dx.doi.org/10.1152/ajprenal.2000.279.4.F671] [PMID: 10997917]
[http://dx.doi.org/10.1016/S0735-1097(01)01492-9] [PMID: 11583890]
[http://dx.doi.org/10.1161/01.CIR.0000085067.55901.89] [PMID: 12912818]
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306301] [PMID: 26892962]
[http://dx.doi.org/10.1161/CIRCRESAHA.107.150417] [PMID: 17702980]
[http://dx.doi.org/10.1002/mrm.10372] [PMID: 12594743 ]
[http://dx.doi.org/10.1038/ijo.2012.170] [PMID: 23069666]
[http://dx.doi.org/10.1016/j.trsl.2009.01.008] [PMID: 19375682]
[http://dx.doi.org/10.1016/S1098-3597(05)80065-1] [PMID: 16473258]
[http://dx.doi.org/10.3390/nu5030928] [PMID: 23507795]
[http://dx.doi.org/10.2174/157016111796642698] [PMID: 21595629]
[http://dx.doi.org/10.2174/157016111796642661] [PMID: 21595628]
[http://dx.doi.org/10.1038/nrcardio.2013.140] [PMID: 24060958]
[http://dx.doi.org/10.1194/jlr.R009720] [PMID: 21041806]
[http://dx.doi.org/10.1016/j.pop.2012.11.003] [PMID: 23402469]
[http://dx.doi.org/10.1097/MED.0000000000000137] [PMID: 25692926 ]
[http://dx.doi.org/10.1161/01.CIR.98.14.1472]
[http://dx.doi.org/10.1161/01.CIR.67.5.968] [PMID: 6219830]
[http://dx.doi.org/10.1093/eurheartj/ehu274] [PMID: 25053660]
[PMID: 26796832]
[http://dx.doi.org/10.2174/13816128113199990303] [PMID: 23286435]
[http://dx.doi.org/10.2174/1389450119666171205101401] [PMID: 29210646]
[http://dx.doi.org/10.1155/2015/971453] [PMID: 25949827]
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.05.917] [PMID: 24908240]
[http://dx.doi.org/10.1161/01.CIR.0000129304.98566.D8] [PMID: 15159289]
[http://dx.doi.org/10.1001/jama.285.19.2486] [PMID: 11368702]
[http://dx.doi.org/10.1161/CIR.0b013e3182160726] [PMID: 21502576]
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306249] [PMID: 26892957]
[http://dx.doi.org/10.1111/bph.13805] [PMID: 28369752]
[http://dx.doi.org/10.1194/jlr.M600390-JLR200] [PMID: 17308299]
[http://dx.doi.org/10.1016/S0021-9150(97)00109-3] [PMID: 9258404 ]
[http://dx.doi.org/10.1172/JCI115532] [PMID: 1752961]
[http://dx.doi.org/10.1161/hc0902.104353] [PMID: 11877368]
[http://dx.doi.org/10.1007/s00018-018-2859-z] [PMID: 29946805]
[http://dx.doi.org/10.1152/ajpheart.00962.2008] [PMID: 19112095]
[http://dx.doi.org/10.1016/j.ccl.2017.12.013] [PMID: 29609761]
[http://dx.doi.org/10.1093/cvr/cvu139] [PMID: 24935432]
[http://dx.doi.org/10.1016/j.amjcard.2012.11.020] [PMID: 23266073]
[http://dx.doi.org/10.1001/jama.2012.9624] [PMID: 22910756]
[http://dx.doi.org/10.1111/bph.13517] [PMID: 27187006]
[http://dx.doi.org/10.1177/1479164118779924] [PMID: 29871496]
[http://dx.doi.org/10.1038/nrcardio.2013.80] [PMID: 23736519]
[http://dx.doi.org/10.1080/14656566.2018.1428560] [PMID: 29334477]
[http://dx.doi.org/10.1126/science.1059344] [PMID: 11349148]
[http://dx.doi.org/10.1016/j.pharmthera.2014.06.003] [PMID: 24928320]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.813311] [PMID: 19075102]
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308537] [PMID: 28057795]
[http://dx.doi.org/10.1056/NEJMoa040583] [PMID: 15007110]
[http://dx.doi.org/10.1016/j.jacc.2007.02.025] [PMID: 17394957]
[http://dx.doi.org/10.1161/01.CIR.95.5.1126] [PMID: 9054840]
[http://dx.doi.org/10.1016/S0735-1097(97)00537-8] [PMID: 9502654]
[http://dx.doi.org/10.1016/S1474-4422(09)70058-4] [PMID: 19375663]
[http://dx.doi.org/10.1016/j.ijcard.2012.04.054] [PMID: 22560909]
[http://dx.doi.org/10.1097/HCO.0000000000000519] [PMID: 29601328]
[http://dx.doi.org/10.1007/s42000-018-0058-9] [PMID: 30229482]
[http://dx.doi.org/10.1185/03007990802469102] [PMID: 18826752]
[http://dx.doi.org/10.2174/1381612822666160701073452] [PMID: 27396601]
[http://dx.doi.org/10.1038/nature01323] [PMID: 12490960]
[http://dx.doi.org/10.1038/79510] [PMID: 10973320]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.630194] [PMID: 17116771]
[http://dx.doi.org/10.1161/01.STR.0000181077.84981.11] [PMID: 16141422]
[http://dx.doi.org/10.1124/mol.59.3.646] [PMID: 11179461]
[http://dx.doi.org/10.1016/j.cardiores.2005.07.002] [PMID: 16098957]
[http://dx.doi.org/10.1089/ars.2013.5537] [PMID: 23924077]
[http://dx.doi.org/10.1161/01.CIR.0000065601.83526.3E] [PMID: 12719275]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.525774] [PMID: 16043642]
[http://dx.doi.org/10.1161/hc2401.092816] [PMID: 11413075]
[http://dx.doi.org/10.1161/01.ATV.20.1.61] [PMID: 10634801]
[http://dx.doi.org/10.1161/01.ATV.0000063385.12476.A7] [PMID: 12615672]
[http://dx.doi.org/10.2174/157489012799362386] [PMID: 22280336 ]
[http://dx.doi.org/10.1161/01.CIR.0000091084.46500.BB] [PMID: 12963641]
[http://dx.doi.org/10.1016/j.jacc.2008.02.066] [PMID: 18582631]
[http://dx.doi.org/10.5551/jat.9084] [PMID: 21921413]
[PMID: 19779116]
[http://dx.doi.org/10.2174/157016105774329453] [PMID: 16248783]
[http://dx.doi.org/10.1080/09537100050129288] [PMID: 11030461]
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.05.022] [PMID: 26074317]
[http://dx.doi.org/10.1038/srep09902] [PMID: 25970700]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.029223] [PMID: 21844076]
[http://dx.doi.org/10.1056/NEJMoa0706201] [PMID: 17984166]
[http://dx.doi.org/10.1016/S0140-6736(08)61240-4] [PMID: 18757089]
[http://dx.doi.org/10.1016/j.amjcard.2009.07.055] [PMID: 19962481]
[http://dx.doi.org/10.1007/s10557-013-6496-3] [PMID: 24158248 ]
[http://dx.doi.org/10.1093/cvr/cvx197] [PMID: 29036612]
[http://dx.doi.org/10.1161/CIR.0b013e31820a55f5] [PMID: 21262990]
[http://dx.doi.org/10.1016/j.amjmed.2011.04.010] [PMID: 21722862]
[http://dx.doi.org/10.1016/j.jacc.2017.10.080] [PMID: 29301631]
[http://dx.doi.org/10.1016/j.jacc.2013.11.002] [PMID: 24239923]
[PMID: 25340243]
[http://dx.doi.org/10.1016/j.cjca.2016.07.510] [PMID: 27712954]
[http://dx.doi.org/10.1001/jama.2016.15450] [PMID: 27838723]
[http://dx.doi.org/10.1093/eurheartj/ehw106] [PMID: 27222591]
[http://dx.doi.org/10.1001/jama.2016.15212] [PMID: 27838724]
[http://dx.doi.org/10.1016/j.atherosclerosissup.2017.05.013] [PMID: 29096858]
[http://dx.doi.org/10.5551/jat.RV17030] [PMID: 30662020]
[http://dx.doi.org/10.1093/eurheartj/ehv043] [PMID: 25694464]
[http://dx.doi.org/10.5114/aoms.2015.49807] [PMID: 25861286]
[http://dx.doi.org/10.1080/03007995.2016.1252740] [PMID: 27776432]
[http://dx.doi.org/10.1016/j.phrs.2016.06.011] [PMID: 27320045]
[http://dx.doi.org/10.1016/j.jacl.2013.04.004] [PMID: 24079286]
[http://dx.doi.org/10.1016/S0021-9150(03)00296-X] [PMID: 14612213]
[http://dx.doi.org/10.1016/S0021-9150(01)00408-7] [PMID: 11500188]
[http://dx.doi.org/10.2174/157016111793744797] [PMID: 21044017]
[http://dx.doi.org/10.1161/ATVBAHA.116.308388] [PMID: 27932353]
[http://dx.doi.org/10.1056/NEJMoa1410489] [PMID: 26039521]
[http://dx.doi.org/10.1345/aph.1M302] [PMID: 19920161]
[http://dx.doi.org/10.1097/01.smj.0000208120.73327.db] [PMID: 16553100]
[http://dx.doi.org/10.1007/s11892-009-0087-5] [PMID: 20425070]
[http://dx.doi.org/10.4065/76.10.971] [PMID: 11605698 ]
[http://dx.doi.org/10.1001/jama.1984.03340270029025] [PMID: 6361299]
[http://dx.doi.org/10.1016/S0021-9150(01)00437-3] [PMID: 11583720]
[http://dx.doi.org/10.1016/S0002-9343(01)00638-6] [PMID: 11286949]
[http://dx.doi.org/10.1038/ng1161] [PMID: 12730697 ]
[http://dx.doi.org/10.1016/j.tibs.2006.12.008] [PMID: 17215125]
[http://dx.doi.org/10.1016/j.jacc.2015.05.001] [PMID: 26088304]
[http://dx.doi.org/10.1056/NEJMoa1500858] [PMID: 25773607]
[http://dx.doi.org/10.1056/NEJMoa1501031] [PMID: 25773378]
[http://dx.doi.org/10.1186/s12916-015-0358-8]
[http://dx.doi.org/10.1016/j.jacl.2018.02.004] [PMID: 29544724]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.028503] [PMID: 28465286]
[http://dx.doi.org/10.1016/S0140-6736(12)61731-0] [PMID: 23122768]
[http://dx.doi.org/10.1016/j.cmet.2016.01.005] [PMID: 26853751]
[http://dx.doi.org/10.1080/14656566.2017.1340941] [PMID: 28598687]
[http://dx.doi.org/10.1056/NEJMoa1615758] [PMID: 28306389]
[http://dx.doi.org/10.1194/jlr.M012872] [PMID: 21398511]
[http://dx.doi.org/10.1039/C8FO00348C] [PMID: 29904777]
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.09.030] [PMID: 26448266]