Role of MicroRNAs in homocysteine induced oxidative stress

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MicroRNAs (miRs) are a novel class of short, non‐coding, endogenous RNA molecules that negatively modulate gene expression primarily through base pairing at 3' untranslated region of target RNA causing mRNA cleavage or translational repression. Homocysteine (Hcy) is a thiol‐containing amino acid and elevated level (hyperhomocysteinemia‐HHcy) causes oxidative stress, one of the central causes of cardiovascular disease. We hypothesize that disregulation of miRs causes oxidative stress in HHcy. To test this hypothesis, we cultured HL1 cardiomyocytes and treated them with different doses of Hcy. Message from oxido‐redox enzymes were determined by RT‐ PCR and Western Blot. MicroRNA array was used to assess the differential expression of miRs in HHcy cardiomyocytes which were further confirmed by individual miR assay. The results suggest that in HHcy cardiomyocytes miR‐188 (‐3p and ‐5p) were dramatically down regulated. Individual miR assay also confirmed it. MMP‐9 which is a signature of extracellular matrix (ECM) remodeling was increased in HHcy cardiomyocytes. These findings suggest the role of miR‐188 in Hcy induced oxidative stress leading to ECM remodeling.