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Aging and disease    2019, Vol. 10 Issue (2) : 353-366     DOI: 10.14336/AD.2018.0617
Review Article |
MicroRNAs or Long Noncoding RNAs in Diagnosis and Prognosis of Coronary Artery Disease
Yuan Zhang*, Lei Zhang, Yu Wang, Han Ding, Sheng Xue, Hongzhao Qi, Peifeng Li*
Institute for Translational Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China
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Abstract  

Coronary artery disease (CAD) is the result of atherosclerotic plaque development in the wall of the coronary arteries. The underlying mechanism involves atherosclerosis of the arteries of the heart which is a relatively complex process comprising several steps. In CAD, atherosclerosis induces functional and structural changes. The pathogenesis of CAD results from various changes in and interactions between multiple cell types in the artery walls; these changes mainly include endothelial cell (EC) dysfunction, vascular smooth muscle cell (SMC) alteration, lipid deposition and macrophage activation. Various blood markers associated with an increased risk for cardiovascular endpoints have been identified; however, few have yet been shown to have a diagnostic impact or important clinical implications that would affect patient management. Noncoding RNAs, especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), can be stable in plasma and other body fluids and could therefore serve as biomarkers for some diseases. Many studies have shown that some miRNAs and lncRNAs play key roles in heart and vascular development and in cardiac pathophysiology. Thus, we summarize here the latest research progress, focusing on the molecular mechanism of miRNAs and lncRNAs in CAD, with the intent of seeking new targets for the treatment of heart disease.

Keywords miRNAs      lncRNAs      coronary artery disease      atherosclerotic plaque     
Corresponding Authors: Zhang Yuan,Li Peifeng   
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These authors contributed equally to this study.

Issue Date: 12 February 2018
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Yuan Zhang
Lei Zhang
Yu Wang
Han Ding
Sheng Xue
Hongzhao Qi
Peifeng Li
Cite this article:   
Yuan Zhang,Lei Zhang,Yu Wang, et al. MicroRNAs or Long Noncoding RNAs in Diagnosis and Prognosis of Coronary Artery Disease[J]. Aging and disease, 2019, 10(2): 353-366.
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http://www.aginganddisease.org/EN/10.14336/AD.2018.0617     OR     http://www.aginganddisease.org/EN/Y2019/V10/I2/353
ClassificationsMiRNAsCell type/processDysfunction typeExpressionFunctionsRefs
ECs/VSMCs functionmiR-126-5pPlasma/ ECsRegulationDown-regulatedplay the role of anti-atherogenisis and enhance ECs repair[27, 28]
miR-17-92 cluster (miR-17, miR-18a, miR-20a, miR-19a/b)Plasma/ ECsRegulationDown-regulatedattenuate TNF-α-induced endothelial cell apoptosis[29, 30]
miR-206VSMCs/ plasmaRegulationUp-regulatedanti-atherosclerosis by inhibiting the expression of FOXP1 in VSMCs[31, 32]
miR-574-5pVSMCs/ plasmaExpressionUp-regulatedpromote cell proliferation and inhibits apoptosis by inhibiting ZDHHC14 gene expression[34]
miR-23aECsRegulationDown-regulatedsuppress cellular migration and vasculogenesis via targeting EGFR[35, 37]
miR-21VSMCsRegulationUp-regulatedpromote aberrant VSMCs proliferation[35, 36]
miR-361-5pPlasma/ ECsRegulationUp-regulatedsuppress VEGF expression and EPCs activity[37]
InflammatorymiR-146aECsRegulationUp-regulatedinhibit the expression of adhesion molecules and inflammatory cytokines[40, 41]
miR-10aECsRegulationDown-regulatedregulate inflammatory responses[42, 43]
miR-155Macrophages/
SMCs
RegulationDown-regulatedfunction as anti-angiogenesis via suppression of AT1R and promote inflammatory signal transduction[44, 45]
miR-22PBMCsRegulationDown-regulatedanti-inflammatory response by targeting MCP-1[46]
Lipid metabolismmiR-486, miR-92aPlasma/ ECsRegulationUp-regulatedparticipate in HDL biogenesis[47, 48]
miR-24, miR-103aPBMCsExpressionUp-regulatedparticipate in cholesterol synthesis/transport and fatty acid metabolism[49]
miR-208aPlasma/ ECsRegulationUp-regulatedregulate cardiac hemostasis and lipid metabolism[51]
miR-370, miR-122PlasmaRegulationUp-regulatedregulate cholesterol and fatty-acid metabolism[51, 52]
miR-93Serum/ ECsRegulationUp-regulatedregulate serum cholesterol level via targeting ABCA1[52]
miR-33aSerum/ ECs macropahgeRegulationUp-regulatedregulate cholesterol accumulation by affecting HDL biogenesis[50]
miR-17-5pPlasma/ macropahgeExpressionUp-regulatedattenuate atherosclerotic lesion by mediating autophagy pathway and regulate cholesterol efflux[53, 54]
Platelet functionmiRNA-223, miRNA-197SerumRegulationUp-regulatedregulate thrombocyte activation[55, 56]
miR-624*, miR-340*PlateletExpressionUp-regulatedgovern platelet reactivity[57]
Circulating miRNAsmiR-126Circulating MVsRegulationDown-regulatedregulate the proliferation and migration of ECs[25]
miR-199aCardiomyocyte/ MVsRegulationDown-regulatedact as a suppressor of cardiomyocyte autophagy[25]
miR-222Endothelial MPsRegulationDown-regulatedanti-inflammatory by inhibiting ICAM-1 expression[63]
miR-149, miR-424PlasmaExpressionDown-regulatedinhibit pro-inflammatory-induced angiogenesis[58, 59]
miR-765Plasma/ ECsExpressionUp-regulatedinfluence arterial stiffness through modulating apelin expression[58]
miR-487aSerumExpressionUp-regulatedinvolve in the occurrence of atherosclerosis by regulating TAB3 expression[61]
miR-502SerumExpressionUp-regulatedsuppress autophagy process and play an atheroprotective role[61]
miR-215Serum/ ECsExpressionUp-regulatedstimulate neointimal lesion formation[61]
miR-29bSerum/ ECsExpressionDown-regulatedregulate myocardial ischemia and cardiac remodeling[62]
miR-145Plasma/VSMCsRegulationDown-regulatedplay a role in VSMCs phenotypic modulation[44]
let-7cPlasma/ECsRegulationDown-regulatedregulate cell differentiation and promote ECs apoptosis by inhibiting of Bcl-xl[44. 60]
Table 1  Summary of coronary artery disease-related miRNAs.
ClassificationsLncRNAsCelltype/processAction modeExpressionFunctionsRefs
ECs/VSMCs functionANRILVSMCAntisenseDown-regulatedregulate expression of CDKN2B and modulate VSMCs proliferation[67, 68]
H19PBMCs/ VSMCs/PlasmaAntisenseUp-regulatedfunction as a sponge of the let-7 to protect VSMCs[69-71]
HIF1a-AS1ECs/VSMCsAntisenseUp-regulatedpartake in process of atherosclerosis through controlling VSMCs and ECs apoptosis[72, 73]
LincRNA-p21ECs/VSMCsLincRNADown-regulateda novel regulator of neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity[74, 75]
RNCR3ECs/ VSMCsLincRNAUp-regulatednegatively regulate hypercholesterolemia and inflammatory factor releases, suppress apoptosis of ECs and VSMCs[76]
TGFB2-OT1ECs/VSMCsceRNAUp-regulatedregulate autophagy in ECs and VSMCs[77]
Lnc-Ang362VSMCsIntronic lncRNAUp-regulatedcoregulate in response to Ang II to regulate VSMCs proliferation[78]
HAS2-AS1VSMCsAntisenseUp-regulatedstabilize or augment the expression of HAS2 mRNA involved in neointimal hyperplasia and inflammation[79]
SMILRVSMCslincRNAUp-regulatedremodel of the extracellular matrix and neointimal formation, and inflammation[80]
SENCRECsAntisenseDown-regulatedregulate endothelial differentiation and angiogenesis[81]
MEG3ECsIntronic lncRNADown-regulatedregulate endothelial differentiation[82]
InflammatoryLincRNA-Cox2ECslincRNAUp-regulatedpromote inflammatory gene transcription in macrophages[84]
MKI67IP-3ECsceRNADown-regulatednegatively regulate let-7e to regulate endothelial function and inflammation[85]
LncRNA-letheMacrophagesceRNADown-regulatednegatively regulate NF-kB expression[86]
Lipid metabolismLincRNA-DYNLRB2-2MacrophageslincRNAUp-regulatedpromote ABCA1-mediated inflammation and cholesterol efflux in foam cells[87]
RP5-833A20.1MacrophagesAntisenseDown-regulatedregulate cholesterol homeostasis and inflammatory reactions through inhibit NFIA expression[88]
APOA1-ASPlasmaAntisenseUp-regulatedinhibit the expression of APOA1 and the formation of HDL[89]
HOTAIRMacrophages/ ECsAntisenseDown-regulatedattenuate the suppression of cell viability and enhancement of cell apoptosis caused by ox-LDL[91, 92]
Circulating lncRNAsCoroMarkerPlasma/
Macrophages
LncRNAUp-regulateddecrease pro-inflammatory cytokine secretion from THP-1 monocytic cells[93, 94]
LncPPARδPBMCsLncRNAUp-regulatedregulate the expression of PPARδ to mediate inflammatory response[95]
LIPCARPlasmaMitochondrial lncRNAUp-regulatedregulate mitochondrial pathways of oxidative phosphorylation and inflammasome activation[71, 96]
Table 2  Summary of coronary artery disease-related lncRNAs.
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