Modulation of apoptosis‐related microRNAs following myocardial infarction in fat‐1 transgenic mice vs wild‐type mice

Abstract

BackgroundmicroRNAs (miRNAs) post‐transcriptionally regulate cardiac repair following myocardial infarction (MI). Omega‐3 polyunsaturated fatty acid (ω‐3 PUFAs) may support cardiac healing after MI, but the mechanism is unclear.MethodsThe fat‐1 transgenic mouse expresses a ω‐3 fatty acid desaturase which converts ω‐6 PUFAs to ω‐3 PUFAs in vivo. MI was induced in fat‐1 transgenic (n = 30) and wild‐type (WT) mice (n = 30) using permanent ligation. Other transgenic and WT mice underwent sham procedure (n = 30 and n = 30, respectively). One week after occlusion, cardiac function was measured by echocardiography and the infarct size was assessed using histology and miRNA microarray profiling. Expression of selected miRNA was confirmed using quantitative real‐time PCR.ResultsOne week following MI, the fat‐1 transgenic myocardium had better cardiac function, a smaller fibrotic area, and fewer apoptotic cardiomyocytes than WT myocardium. Post‐MI profiling showed 33 miRNAs that were significantly up‐regulated, and 35 were down‐regulated, in fat‐1 group compared to the WT group (n = 3 and n = 2 mice, respectively). Among selected apoptosis‐associated miRNAs, 9 miRNAs were up‐regulated (miR‐101a‐3p, miR‐128‐3p,miR‐133a‐5p,miR‐149‐5p,miR‐192‐5p,miR‐1a‐3p,miR‐208a‐3p,miR‐29c‐5p,miR‐30c‐2‐3p), and 3 were down‐regulated (miR‐210‐3p,miR‐21a‐3p,miR‐214‐3p) in fat‐1 transgenic mice compared with WT mice. Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated likely roles for these miRNAs in MI. Furthermore, Bcl‐2 expression was increased, and caspase‐3 decreased, in infarcted fat‐1 transgenic mouse hearts compared to WT hearts.Conclusionsω‐3 PUFAs may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis‐related miRNAs and target genes.

The Influence of Diet on MicroRNAs that Impact Cardiovascular Disease

“…Downregulation of miRNA-21 after consumption of PUFAs was also observed in other studies of animal models and cell cultures [100,101]. Ma et al [102] concluded that omega-3 PUFAs may have a protective effect on cardiomyocytes following myocardial infarction through their upregulation of anti-apoptotic miRNAs (miRNA-133a-5p, miRNA-149-5p, miRNA-208a-3p) and downregulation of pro-apoptotic miRNAs (miRNA-210-3p). Zheng et al [94] reported that omega-3 PUFAs regulate miRNA-19b, -146b and -183 in Wistar rats.…”

Cardioprotective Effects of Dietary Flaxseed Post-Infarction Are Associated with Changes in MicroRNA Expression

“…Various nutritional components can modulate the expression of diverse miRNAs [ 3 ]. Omega-3 PUFAs, for example, protect cardiomyocytes after an MI by upregulating the anti-apoptotic miRNAs and downregulating the pro-apoptotic miRNAs [ 28 , 29 ]. Flaxseed is the richest source of the plant-based omega-3 PUFA, ALA. Dietary supplementation with flaxseed has demonstrated anti-arrhythmic, antiatherogenic, antihypertensive, and cholesterol-lowering effects in animal and human studies [ 21 ].…”

Serum microRNA-204 Levels are Associated with Long-Term Cardiovascular Diseases Risk Using Framingham Risk Score in Patients with Type 2 Diabetes: Results From an Observational Study

“…Previous investigations have shown that miRNAs played important roles in physiological and pathological processes, including cell cycle regulation [1], cell differentiation [1] in ammatory responses [2], apoptosis [3] and extracellular matrix (ECM) degradation [4]. Upgraded serum miRNA-204 (miR-204) levels have been regarded as associated with insulinoma [5], acute lymphocytic leukemia [6], human breast cancer [7] and other tumors [8].…”