Abstract
Coronary artery disease (CAD) is the leading cause of mortality globally. Although substantial advances have been made in the diagnosis, management, and risk stratification of CAD, there is still a need for novel diagnostic biomarkers and new therapeutic targets to prevent the epidemic of the disease. Recently, growing evidence has linked dysregulated microRNAs (miRNAs) to cardiovascular diseases, including CAD. miRNAs are endogenous, stable, single-stranded, short, non-coding RNAs, and may have utility as diagnostic and prognostic biomarkers for CAD. Dysregulated miRNAs are involved in regulating lipid and glucose homeostasis pathways, reninangiotensin- aldosterone pathways, inflammation, endothelial and vascular smooth cell phenotypes promoting atherosclerotic plaque development, progression, and instability. Additionally, miRNAs are stable and easily accessible in the extracellular space, may reside in microvesicles, and are detectable in serum or plasma, making them attractive biomarkers for the diagnosis and prognosis of cardiovascular disease. Accumulating studies suggest that miRNAs could be useful biomarkers for early discrimination of patients presenting with myocarditis or Takotsubo syndrome from those with a diagnosis of acute myocardial infarction, early prognostication of patients presenting with acute coronary syndromes, and accurate detection of left ventricular remodeling after a chronic or acute ischemic event. Moreover, miRNAs represent potential novel therapeutic targets for CAD or other cardiovascular diseases. This review provides an overview of the effects of the entire spectrum of CAD, its major risk factors, and complications on levels of circulating miRNAs, as well as the limitations and challenges of their potential clinical applications.
Graphical Abstract
[http://dx.doi.org/10.1016/S0140-6736(18)32203-7] [PMID: 30496103]
[http://dx.doi.org/10.1093/cvr/cvz302] [PMID: 31782762]
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306300] [PMID: 26892968]
[http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621]
[http://dx.doi.org/10.1101/gr.082701.108] [PMID: 18955434]
[http://dx.doi.org/10.1016/j.cell.2005.07.031] [PMID: 16122423]
[http://dx.doi.org/10.1002/1873-3468.13085] [PMID: 29749606]
[http://dx.doi.org/10.1016/j.trecan.2018.05.002] [PMID: 29937044]
[http://dx.doi.org/10.1093/cvr/cvr266] [PMID: 22028337]
[http://dx.doi.org/10.1093/clinchem/48.10.1647] [PMID: 12324479]
[http://dx.doi.org/10.1038/ncb2210] [PMID: 21423178]
[http://dx.doi.org/10.1093/nar/gkr254] [PMID: 21609964]
[http://dx.doi.org/10.1186/gb-2014-15-4-r57] [PMID: 24708865]
[http://dx.doi.org/10.1093/nar/gkt1181] [PMID: 24275495]
[http://dx.doi.org/10.1093/nar/gkm952] [PMID: 17991681]
[http://dx.doi.org/10.1093/eurheartj/ehab484] [PMID: 34458905]
[http://dx.doi.org/10.1038/nature06783] [PMID: 18368051]
[http://dx.doi.org/10.1016/j.cmet.2006.01.005] [PMID: 16459310]
[http://dx.doi.org/10.1128/MCB.00470-19] [PMID: 32071155]
[http://dx.doi.org/10.1093/cvr/cvaa039] [PMID: 32061123]
[http://dx.doi.org/10.1161/01.HYP.0000217521.79447.9a] [PMID: 16567584]
[http://dx.doi.org/10.1111/j.1399-0004.1997.tb02410.x] [PMID: 9084931]
[http://dx.doi.org/10.1086/519979] [PMID: 17668390]
[http://dx.doi.org/10.1038/s41440-020-0453-x] [PMID: 32427944]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13412] [PMID: 31352819]
[http://dx.doi.org/10.1038/s41440-018-0071-z] [PMID: 29973661]
[http://dx.doi.org/10.1038/s41440-020-0492-3] [PMID: 32555411]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.180729] [PMID: 22042811]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01701] [PMID: 23897069]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.023926] [PMID: 27542393]
[http://dx.doi.org/10.3109/10641963.2015.1036064] [PMID: 26114349]
[http://dx.doi.org/10.1016/j.diabres.2019.107843]] [PMID: 31518657]
[http://dx.doi.org/10.1093/cvr/cvr300] [PMID: 22065734]
[http://dx.doi.org/10.1038/nature03076] [PMID: 15538371]
[http://dx.doi.org/10.1016/j.ebiom.2016.12.002] [PMID: 27974246]
[http://dx.doi.org/10.1038/ijo.2015.95] [PMID: 25999046]
[http://dx.doi.org/10.1080/09674845.2017.1402404] [PMID: 29452547]
[http://dx.doi.org/10.1186/s12933-016-0367-8] [PMID: 27005938]
[http://dx.doi.org/10.1080/13813455.2019.1651340] [PMID: 31392905]
[http://dx.doi.org/10.1016/j.cca.2010.09.029] [PMID: 20888330]
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.07.020] [PMID: 21820659]
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309318] [PMID: 27895035]
[http://dx.doi.org/10.1161/ATVBAHA.118.311942] [PMID: 30587001]
[http://dx.doi.org/10.1016/j.atherosclerosis.2019.10.003] [PMID: 31704554]
[http://dx.doi.org/10.1161/01.CIR.0000105763.51286.7F] [PMID: 14662709]
[http://dx.doi.org/10.1016/j.jacc.2014.01.050] [PMID: 24583309]
[http://dx.doi.org/10.1373/clinchem.2010.144121] [PMID: 20395621]
[http://dx.doi.org/10.3892/mmr.2016.5495] [PMID: 27430349]
[http://dx.doi.org/10.1111/joim.12921] [PMID: 31141242]
[http://dx.doi.org/10.1038/nature03817] [PMID: 15951802]
[PMID: 20163779]
[http://dx.doi.org/10.1038/nm1569] [PMID: 17401374]
[http://dx.doi.org/10.15212/CVIA.2016.0042]
[http://dx.doi.org/10.1093/eurheartj/eht392] [PMID: 24046434]
[http://dx.doi.org/10.1093/cvr/cvab210] [PMID: 34155498]
[http://dx.doi.org/10.1056/NEJMoa2003608] [PMID: 34042389]
[http://dx.doi.org/10.18632/aging.103320] [PMID: 32554856]
[http://dx.doi.org/10.1159/000479995] [PMID: 28817807]
[PMID: 31799683]
[http://dx.doi.org/10.1371/journal.pone.0145930] [PMID: 26720041]
[http://dx.doi.org/10.1097/MD.0000000000018049] [PMID: 31764830]
[http://dx.doi.org/10.1253/circj.CJ-14-0958] [PMID: 25519160]
[http://dx.doi.org/10.1136/openhrt-2019-001223] [PMID: 32487772]
[PMID: 32377580]
[http://dx.doi.org/10.1152/physiolgenomics.00071.2021] [PMID: 35226566]
[http://dx.doi.org/10.1055/s-0039-1700518] [PMID: 31715633]
[http://dx.doi.org/10.1042/BSR20160023] [PMID: 27190129]
[http://dx.doi.org/10.1093/eurheartj/ehv508] [PMID: 26419623]
[http://dx.doi.org/10.1161/01.CIR.0000065118.99409.5F] [PMID: 12756191]
[http://dx.doi.org/10.1093/eurheartj/ehr308] [PMID: 21969521]
[http://dx.doi.org/10.1155/2016/4285942] [PMID: 28050558]
[http://dx.doi.org/10.1016/j.lfs.2018.06.001] [PMID: 29870767]
[http://dx.doi.org/10.1038/s41598-017-01695-3] [PMID: 28484274]
[http://dx.doi.org/10.1371/journal.pone.0137035] [PMID: 26331273]
[PMID: 30476011]
[http://dx.doi.org/10.1002/ccd.21715] [PMID: 19021281]
[http://dx.doi.org/10.1016/j.ijcard.2016.07.209] [PMID: 27499222]
[http://dx.doi.org/10.1161/JAHA.118.011190] [PMID: 30764687]
[PMID: 33960307]
[http://dx.doi.org/10.1007/s12265-020-10020-9] [PMID: 32458401]
[http://dx.doi.org/10.5603/CJ.a2020.0034] [PMID: 32207842]
[http://dx.doi.org/10.1016/j.yexmp.2020.104522] [PMID: 32866521]
[http://dx.doi.org/10.4103/0366-6999.196573] [PMID: 28051023]
[http://dx.doi.org/10.1536/ihj.18-306] [PMID: 30745540]
[http://dx.doi.org/10.1371/journal.pone.0070644] [PMID: 23967079]
[http://dx.doi.org/10.1161/CIRCGENETICS.113.000077] [PMID: 23547171]
[http://dx.doi.org/10.1016/j.ijcard.2014.07.068] [PMID: 25124998]
[http://dx.doi.org/10.1016/j.yjmcc.2011.07.011] [PMID: 21806992]
[http://dx.doi.org/10.1016/j.ahj.2012.08.004] [PMID: 23137501]
[http://dx.doi.org/10.1016/j.amjcard.2017.03.264] [PMID: 28511772]
[http://dx.doi.org/10.1016/j.bbrc.2012.09.039] [PMID: 22995291]
[http://dx.doi.org/10.3390/ijms15045774] [PMID: 24714087]
[http://dx.doi.org/10.1155/2018/2410451] [PMID: 29977411]
[http://dx.doi.org/10.7754/Clin.Lab.2016.160632]] [PMID: 28164501]
[http://dx.doi.org/10.1007/s11010-014-2089-0] [PMID: 24833470]
[PMID: 27357355]
[http://dx.doi.org/10.1016/j.ijcard.2019.05.008] [PMID: 31085080]
[http://dx.doi.org/10.1155/2021/2923441] [PMID: 34786024]
[http://dx.doi.org/10.1186/s12933-015-0274-4] [PMID: 26285575]
[http://dx.doi.org/10.1016/j.cjca.2020.03.018] [PMID: 32735867]
[PMID: 28011706]
[http://dx.doi.org/10.1253/circj.CJ-16-0568] [PMID: 27593229]
[http://dx.doi.org/10.3389/fphys.2019.00686] [PMID: 31231239]
[http://dx.doi.org/10.1042/CS20100003] [PMID: 20524934]
[http://dx.doi.org/10.1038/s41401-018-0041-7] [PMID: 29891858]
[http://dx.doi.org/10.1007/s11845-020-02196-5] [PMID: 32064546]
[http://dx.doi.org/10.1186/s12872-021-01891-0] [PMID: 33546604]
[http://dx.doi.org/10.2217/bmm-2019-0257] [PMID: 31789049]
[http://dx.doi.org/10.1161/JAHA.114.001249] [PMID: 25349183]
[http://dx.doi.org/10.3109/00365513.2014.981855] [PMID: 25465803]
[http://dx.doi.org/10.12659/MSM.912065] [PMID: 30192743]
[http://dx.doi.org/10.1159/000509275] [PMID: 33730720]
[http://dx.doi.org/10.1002/ctm2.585] [PMID: 35167732]
[http://dx.doi.org/10.1038/s41598-022-06923-z] [PMID: 35228564]
[PMID: 28272697]
[http://dx.doi.org/10.1159/000477235] [PMID: 28618412]
[http://dx.doi.org/10.21037/qims-19-829] [PMID: 32676367]
[http://dx.doi.org/10.1016/j.ijcard.2017.06.054] [PMID: 28663047]
[http://dx.doi.org/10.1038/s41598-018-28118-1] [PMID: 29959359]
[PMID: 30088484]
[http://dx.doi.org/10.5301/heartint.5000226] [PMID: 27924211]
[http://dx.doi.org/10.1155/2019/2925019] [PMID: 31781298]