Pregnancy-associated cardiac dysfunction and the regulatory role of microRNAs

Aryan, Laila; Medzikovic, Lejla; Umar, Soban; Eghbali, Mansoureh

doi:10.1186/s13293-020-00292-w

Biology of Sex Differences

Table 2 Differentially expressed circulating miRNAs in preeclampsia and their effects in heart disease

From: Pregnancy-associated cardiac dysfunction and the regulatory role of microRNAs

miRNA	Regulation in human pregnancy	Ref.	Heart disease	Mechanism and outcome	Ref.
miR-210-3p and miR-210-5p	↑ serum	[160,161,162,163]	Hypoxic cardiomyocytes, mouse and rat	↑ Akt → ↑ miR-210 → ↓ PDCD4 → ↓ ROS, ↓ cell death	[164, 165]
			Mouse LAD ligation	↑ miR-210-3p → ↓ APC → ↓ cardiomyocyte apoptosis, ↑ angiogenesis, ↑cardiac function	[166]
			Mouse LAD ligation	↑ miR-210-3p in mesenchymal stem cells-derived extracellular vesicles → ↓ Efna3 → promote cardiac angiogenesis post-MI	[167]
miR-29a	↑ plasma	[168]	Patients with hypertrophic cardiomyopathy	↑ miR-29a → ↑ cardiac hypertrophy, ↑fibrosis	[169, 170]
			Mouse TAC	↓ miR-29a → ↓ cardiac hypertrophy, ↓fibrosis	[170]
			ET-1 in H9c2 cardiomyocytes	↓ NFATc4 → ↓ cardiomyocyte hypertrophy	[171]
miR-21	↑ plasma	[160]	Mouse, cardiac fibroblast-derived exosomes	↑ crosstalk between cardiac fibroblasts and cardiomyocytes → ↑ cardiomyocyte hypertrophy	[172]
			Mouse TAC	↓ Spry1, ↑ ERK-MAPK activity → ↑ fibroblast survival, ↑ growth factor secretion → ↓ fibrosis, ↓ cardiac hypertrophy	[172]
			Mouse post-MI via LAD ligation	↓ SMAD7 → ↑ cardiac fibrosis post-MI	[173]
			Rat IRI	↓ PDCD4 → ↓ apoptosis post-MI	[174]
			Mouse LAD ligation	↓ miR-21 → targets KBTBD7 (p38 MAPK and NFκB modulator) → ↓ cardiac dysfunction/inflammatory signaling	[175]
miR-155	↑ plasma	[160]	miR-155-KO mice TAC	↓ miR-155 → ↑ jumonji/Jarid2 → ↓ cardiac hypertrophy	[176]
			miR-155 KO macrophages	↑ Socs1 → ↑ cardiomyocyte hypertrophy	[177]
			fibroblast miR-155-KO	↓ TP53INP1→ ↑ cardiac remodeling	[178]
miR-206	↑ plasma	[179]	Mouse with TAC-induced cardiac hypertrophy	↑ miR-206 → ↓ tumor suppressor FoxP1→ ↑ TAC-induced cardiac hypertrophy	[180]
miR-144	↓ plasma and ↓ serum	[160, 161, 168]	miR-144-KO mouse LAD ligation	↑ Zeb-1→ impaired fibrotic response post-injury → cardiac dysfunction	[181]
			Mouse LAD ligation	↑ miR-144 mimic injection → ↓ fibrosis, ↓inflammation, ↓apoptosis → ↑cardiac function	[182]
			miR-144-KO mouse	↓ Rac-1 → ↑ ROS	[183]
miR-125b-5p	↓ plasma	[184]	Mouse LAD ligation	↓ bak1, ↓ klf13 → ↓ cardiomyocyte apoptosis	[139]
miR-195-5p	↓ plasma	[184, 185]	Severe PE patients	Unknown mechanism	NA
	↑ plasma	[186]	PE patients	↑ sFLT1 levels	[186]
	↑ plasma	[186]	Mouse Ang II infusion	↑ miR-195-5p → ↓ FBXW7/MFN2 → ↑ mitochondrial membrane depolarization/ROS production → ↑ cardiomyocyte hypertrophy	[187]
miR-126	↓ serum	[161]	miR-126-KO mice LCA ligation	↑ Spred1 → defective angiogenesis	[188]
miR-126	↓ serum	[161]	Human cardiac microvascular endothelial cells	↑ miR-126 → ↑ PI3K/Akt, ↑ VEGF, ↑SOD expression → hypoxia/reoxygenation injury protection	[189]
miR-204	↓ serum	[161]	Mouse LAD ligation	↑ miR-204 → ↓ LC3-II	[190]
miR-15b	↓ serum	[161]	Mouse TAC overload	↑ miR-15b → ↓TGFβ signal(p38 MAPK/TGFβR-1 → ↑ cardiomyocyte hypertrophy, ↑ fibrosis	[191]

Akt protein kinase B, Ang II angiotensin II, APC adenomatous polyposis coli, ECM extracellular matrix, Efna3 angiogenesis modulator ephrin A3, ERK-MAPK extracellular signal-regulated kinases/mitogen-activated protein kinase, ET-1 endothelin 1, FBXW7 F-box and WD repeat domain containing 7, FoxP1 Forkhead box protein P1, IRI ischemia/reperfusion injury, Jarid2 jumonji, AT rich interactive domain 2, KBTBD7 kelch repeat and BTB domain-containing protein 7, KO knockout, LAD left anterior descending, LC3-II microtubule-associated protein 1 light chain 3, LC3-II microtubule-associated protein 1 light chain 3, LCA left coronary artery, MFN2 mitofusion 2, MI myocardial infarction, miR microRNA, NFATc4 nuclear factor of activated T cells 4, NFκB nuclear factor kappa-light-chain-enhancer of activated B cells, p38 MAPK mitogen activated protein kinase p38, PDCD4 programmed cell death protein 4, PE preeclampsia, PI3K/Akt phosphatidylinositol 3-kinase/protein kinase B, RAC-1 Ras-related C3 botulinum toxin substrate 1, ROS reactive oxygen species, sFLT1 fms-like tyrosine kinase 1, SMAD7 small mothers against decapentaplegic 7, Socs1 cytokine signaling 1, SOD superoxide dismutase, Spry1 sprouty RTK signaling antagonist 1, TAC transverse aortic constriction, TGFβR-1 transforming growth factor beta receptor I, TP53INP1 tumor protein p-53-inducible nuclear protein 1, VEGF vascular endothelial growth factor, Zeb-1 zinc finger E-box binding homeobox 1

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ISSN: 2042-6410

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