Mediators of Inflammation

Review Article

Novel Insights into miRNA in Lung and Heart Inflammatory Diseases

Table 4

miRNAs in cardiovascular diseases.


miRNA	Cell/tissue/body fluid (models)	Regulation	Validation method	Predicted target gene/possible effect	References

Atherosclerosis
miR-21	Plaques and arteries (H)	Up	qRT-PCR	Signal transduction; regulation of transcription; vesicular transport	[142, 143]
miR-26, -30, and -125a	Plaque tissue (H)	Up	qRT-PCR	Signal transduction; regulation of transcription; vesicular transport	[144]
miR-34a	Plaques and arteries (H)	Up	qRT-PCR	Signal transduction; regulation of transcription; vesicular transport	[143]
miR-146a	Plaques and arteries (H)	Up	qRT-PCR	Signal transduction; regulation of transcription; vesicular transport	[142, 143, 145]
miR-146b-5p	Plaques and arteries (H)	Up	qRT-PCR	Signal transduction; regulation of transcription; vesicular transport	[143]
miR-181b	Aortic intima (M) and plasma (H)	Down	qRT-PCR	Importin-α3; ⊥NF-κB signalling and atherosclerotic lesion formation	[146]
miR-210	Plaques and arteries (H)	Up	qRT-PCR	Potential biomarker	[143]
miR-712	Mouse arterial endothelial cell (M + C)	Up	qRT-PCR	↓TIMP3; ↑MMPs and ADAMs	[147]
Acute myocardial infarction (AMI)
Let-7b	Plasma (H)	Up	qRT-PCR	Differentiate AMI patients from healthy controls	[148]
miR-1	Plasma (H), serum (M), and rat cardiac cells (R + C)	Up	qRT-PCR	Potential biomarker for AMI	[149–154]
miR-21	Heart (R)	Down	qRT-PCR	Expression signature in early phase of AMI	[155]
miR-30a and -195	Plasma (H)	Down	qRT-PCR	Differentiate AMI patients from healthy controls	[148]
miR-122	Plasma (H)	Down	qRT-PCR	Potential biomarker for AMI	[151, 156]
miR-133a and -b	Plasma and whole blood (H)	Up	qRT-PCR	Potential biomarker for AMI	[150, 151, 154, 156]
miR-133 and -328	Plasma and whole blood (H)	Up	qRT-PCR	Potential biomarker for AMI	[157]
miR-126	Plasma (H)	Down	qRT-PCR	Potential biomarker for AMI	[153]
miR-155	Monocytes, B-cells, T-cells (H), and knockout mice (M)	Up	miRNA profiling and qRT-PCR	TLR- pathway, NF-κB, FADD, Rip-1; proinflammatory miRNA	[158]
miR-208a and -499	Plasma (H)	Up	qRT-PCR	Potential biomarker for AMI	[154, 159, 160]
Cardiac hypertrophy
miR-1	Heart and skeletal muscle (M + R) and coronary artery cells (H)	Down	Nothern blot; qRT-PCR	Twinfilin-2	[161]
miR-21	Heart (M)	Up	Northern blot and qRT-PCR	—	[162]
miR-22	Cardiac and muscle specific (M)	Up	qRT-PCR and western blot	Sirt1 and HDACY	[163]
miR-27b	Cardiomyocytes (M)	Up	Western blot and qRT-PCR	PPAR-	[164]
miR-29a	Plasma (H)	Up	qRT-PCR		[165]
miR-30	Heart (R), cardiac tissue, and plasma (H)	Down	qRT-PCR	Beclin-1; ↑Ang II: ↓miR-30a: ↑Beclin-1: excessive autophagy: myocardial hypertrophy	[166]
miR-133	Human (H), mouse (M), and rat (R) heart	Down	qRT-PCR and northern and western blot	RhoA, Cdc42, Nelf-A/WHSC2	[167, 168]
miR-155	Leukocytes (M)	Up	—	Promotes cardiac inflammation, hypertrophy, and failure	[169]
miR-214	Heart and cardiomyocytes (R)	Up	Luciferase assay and western blot	↑miR-214; ↓EZH2	[136]
Cardiac fibrosis
miR-21	Cardiac fibroblast (H)	Up	—	SPRY1	[170]
miR-21	Cardiac myocytes (M)	Up	qRT-PCR	⊥PTEN; protects against cardiac ischemia/reperfusion Injury	[171, 172]
miR-29	Cells, mouse (M), and human (H) cardiac tissue	Up	miRNA microarray and qRT-PCR	Inflammatory cytokines	[173]
miR-133	Heart (M)	Down	qRT-PCR	Col1A1	[170, 174]
miR-26a	Heart (M)	Down	qRT-PCR	CTGF and Col1A1	[175]
miR-30	Heart (H + R), cardiac fibroblast, and myocytes (R + C)	Up	qRT-PCR	↑miR-30: ↓CTGF	[176]
miR-122	Endomyocardial biopsies (H)	Down	qRT-PCR	⊥TGF-1; progression of myocardial fibrosis in aortic stenosis	[177]
Coronary artery disease (CAD)
miR-17/92a cluster, -126, -145, and -155	Plasma (H)	Down	qRT-PCR	Potential biomarker for CAD	[178]
miR-21	Endothelial cells and vessel wall (H)	Up	qRT-PCR	Potential biomarker for CAD	[179]
miR-106b/25 cluster, -17/92a cluster, -21/590-5p family, -126*, and -451	Plasma (H)	Up	qRT-PCR	May affect inflammation, hypoxia, angiogenesis, apoptosis, and extracellular matrix (ECM) degradation	[180]
miR-126	Endothelial cells and vessel wall (H)	Down	qRT-PCR	Potential biomarker for CAD	[151, 179]
miR-133a	Endothelial cells and vessel wall (H)	Up	qRT-PCR	Potential biomarker for CAD	[179]
miR-135a	PBMC (H)	Up	qRT-PCR	Potential biomarker for CAD	[181]
miR-147	PBMC (H)	Down	qRT-PCR	Potential biomarker for CAD	[181]
miR-155	Endothelial cells and vessel wall (H)	Down	qRT-PCR	Potential biomarker for CAD	[151, 179]
miR-208a	Endothelial cells and vessel wall (H)	Up	qRT-PCR	Potential biomarker for CAD	[151]
miR-221	Endothelial cells and vessel wall (H)	Down	qRT-PCR	Potential biomarker for CAD	[179]
miR-370	Endothelial cells and vessel wall (H)	Up	qRT-PCR	Potential biomarker for CAD	[179]
Heart failure
miR-1	Muscle (H)	Down	qRT-PCR	GATA 14 and MEF2A	[182–184]
miR-16, -20b, -93, -106b, -223, and -423-5p	Plasma (R)	Up	qRT-PCR	Expression level changes during progression of hypertension-induced heart disease	[185]
miR-21	Plasma, muscle, and heart tissue (H)	Up	qRT-PCR	PTEN	[182–184]
miR-23a	Plasma, muscle, and heart tissue (H)	Up	qRT-PCR	MuRF1	[182–184]
miR-29b	Plasma, muscle, and heart tissue (H)	Down	qRT-PCR	Col1A1, Col1A2, and Col3A1	[182–184]
miR-30	Plasma, muscle, and heart tissue (H)	Down	qRT-PCR	CTGF	[176, 182–184]
miR-125	Plasma, muscle, and heart tissue (H)	Up	qRT-PCR	—	[182–184]
miR-126	Plasma (H)	Down	qRT-PCR	Useful biomarker for heart failure	[186]
miR-133	Right atrial appendages (H)	Down	qRT-PCR	CTFG and SRF	[187]
miR-208a	Cardiac tissue and plasma (M + R)		Microarray profiling; qRT-PCR		[188]
miR-210	Plasma (M + H), H9c2 (C), and mononuclear cells (M + H)	Up	qRT-PCR	Repress ISCU, leading to repression of mitochondrial respiration	[189]
miR-423-5p; -320, -22, and -92b	Plasma (H) and serum (H)	Up	qRT-PCR	Positive correlation of miR-423-5p with BNP and NT-proBNP	[190–192]

↑: increased level; ↓: decreased level; ⊥: inhibition. Investigating models: mouse (M), rat (R), cell culture (C), and human (H).A disintegrin and metalloproteases (ADAMs); collagen, type I, alpha 2 (Col1A2); collagen, type III, alpha 1 (Col3A1); connective tissue growth factor (CTGF); cytoplasmic SH2 domain containing protein tyrosine phosphatase (SHP2); enhancer of zeste homolog 2 (EZH2); Fas-associated death domain (FADD); iron-sulfur cluster assembly protein (ISCU); matrix metalloproteinases (MMPs); myocyte enhancer factor 2A (MEF2A); muscle ring-finger protein-1 (MuRF1); nuclear factor-kB (NF-kB); phosphatase and tensin homolog (PTEN); receptor-interacting protein 1 (RIP1); serum response factor (SRF); sirtuin 1 (Sirt1); proliferator-activated-receptor- (PPAR-); sprouty homolog 1 (SPRY1); Toll-like receptor (TLR); tissue inhibitor of metalloproteinase 3 (TIMP3).