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

Background micro RNA s (mi RNA s) post‐transcriptionally regulate cardiac repair following myocardial infarction ( MI ). Omega‐3 polyunsaturated fatty acid (ω‐3 PUFA s) may support cardiac healing after MI , but the mechanism is unclear. Methods The fat‐1 transgenic mouse expresses a ω‐3 fatty acid desaturase which converts ω‐6 PUFA s to ω‐3 PUFA s 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 mi RNA microarray profiling. Expression of selected mi RNA was confirmed using quantitative real‐time PCR . Results One 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 mi RNA s 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 mi RNA s, 9 mi RNA s 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 mi RNA s in MI . Furthermore, Bcl‐2 expression was increased, and caspase‐3 decreased, in infarcted fat‐1 transgenic mouse hearts compared to WT hearts. Conclusions ω‐3 PUFA s may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis‐related mi RNA s and target genes.