Table 1.

Role of selected inflamma-miRs in cardiovascular pathophysiology.

miRNA	Upstream regulation	Targets	Functional effect	Ref
miR-21	LPS	↓PDCD4	Activation of NF-κB or transcription of IL10	19
		↓ SORBS2	Worst outcome in septic cardiomyopathy	24
	Oscillatory shear stress	↓ PPARα	Endothelial cells inflammation	25
	Induced overexpression (miR-21 mimic)	↑ Akt/PKB	NO production, proliferation and apoptosis of endothelial cells	26
	Genetic ablation (miR-21-/-)	↓ ABCG1	Foam cell formation, larger atherosclerotic areas	28
miR-33	SREBP in situations of reduced lipid abundance	↓CPT1A ↓ HADHB ↓ CROT	Reduced cellular cholesterol metabolism	42
	Genetic ablation in macrophages (miR-33-/-)	─	Reduced lipid deposits, inflammation and plaque burden	44
	Genetic ablation in the liver (miR-33-/-)	─	Resistance to hepatic fibrosis and insulin	45
	─	↓ ABCA1	Increased cardiac fibroblast proliferation	47
			Regulated amyloid burden and inflammation in neurons and glia.	48
miR-34a	p53 (positive feedback loop)	↓ SIRT1	Increased acetylated p53 and modulation of apoptosis.	33
	Damaged cardiac microvascular endothelial cells by incubation with homocysteine	↓ NOTCH1	Increased apoptosis and decreased angiogenesis.	35
	Hypoxia in cardiomyocytes	↓ ZEB1	Increased apoptosis.	36
	Genetic ablation (miR-34a-/-) in macrophages	↑ ABCA1 ↑ ABCG1	Reduced cholesterol efflux, reverse cholesterol transport and inhibited atherosclerosis progression in an ApoE-/- mouse model.	37
	Calcific aortic valve disease ↓ NOTCH1	↑ RUNX2	Increased calcium deposition of aortic valves and cardiac hypertrophy.	39
	Myocardial infarction and TGFβ1	↓ SMAD4	Progression of cardiac tissue fibrosis	40
miR-146a	NF-κB	↓ IRAK1 ↓ TRAF6	Fine-tune inflammatory cytokine production	53
	Genetic ablation (miR-146a-/-) and endotoxemic challenge	─	Exaggerated inflammation, multiorganic inflammation, myeloid proliferation, cancer and premature death.	54
	Induced overexpression (miR-146a mimic)	↓ NOX4	Preserved cardiac function and reduced the infarct zone and inflammatory response in an ischemic/reperfusion injury model.	55
	Ischemic/reperfusion injury (↓ miR-146a mitochondrial)	↑ Cyclophilin D	Mitochondrial dysfunction and cardiomyocyte apoptosis.	56
	Genetic ablation (miR-146a-/-) in fat-fed Ldlr-/- mice	↑ SORT1	Increased proinflammatory cytokines and a reduction in atherosclerosis.	58
miR-155	Dietary compounds such as polyunsaturated fatty acids or arachidonic acid (↓ miR-155)	─	Anti-atherogenic effects.	66
	Inflammatory stimuli (NF-κB binds to the promoter of pri-miR-155)	↓ CARHSP1	Shift in macrophages to M1 phenotype.
	LPS-induced sepsis Molecular clock	↓ BMAL1	Disturbed circadian function.	70
	TNF-α	↓ sGCβ1	Reduced contractile capacity of vascular smooth muscle cells and less vasorelaxation.	71
	ox-LDL in macrophages induced TRIF and ERK signaling.	↓ SOCS1	Regulation of macrophage inflammatory response.	72
	miR-155 antagomir (↓ miR-155)	↑ SOCS1		76
	Induced overexpression (miR-155 mimic)	↓ ABCA1 ↓ ABCG1	Reduced cholesterol efflux and increased foam cell formation.	64
	CTRP12 (↓ miR-155) ↑ ABCA1	↑ ABCG1	Inhibition of lipid accumulation and inflammatory response.
	Acute myocardial infarction	─	Decreased apoptosis in cardiomyocytes.	76
miR-223	C/EBP-α or –β and NFI-A negative feedback loop	↓ NFI-A	Increased myeloid cell differentiation.	78
	Cell activation via TLRs	↓ NLRP3	Prevention of IL-1β production.	79
	Plasma HDL by SR-BI-induced lipid flux	Formation of HDL-miR-223 complexes	Control of cholesterol homeostasis and cell-cell intercommunication.	81
	─	↓ ICAM1	Regulates the NF-κB and MAPK signaling pathways in endothelial cells decreasing lipid deposition in the arterial wall and promoting endothelial activation.	84
	Genetic ablation (transplantation with bone marrow miR-223-/- in mice)	↑ SP3 ↓ ABCA1 ↓ RETNLA	Increased atherosclerotic plaques size, lipid levels and IL-1β plasma levels.	85
	Atherosclerosis lesions	↓ MEK1	Stable atherosclerosis lesions and reduced levels of atherosclerotic markers.	86
	Pre-miR-223-/- mice hearts	↑ IKKα pathway ↑ NLRP3	Higher inflammation and necroptosis.	87
	Induced by hypoxia	↓ KLF15	Increased oxidative stress, caspase-3 activation and ROS generation.	88
	─	P2Y12	Regulated platelet reactivity.	89
				90
			Biomarker of the response to antiplatelet drugs.	83, 92 93

↑, upregulated; ↓, downregulated; -, No target associated.