Folic Acid Mitigated Cardiac Dysfunction by Normalizing the Levels of Tissue Inhibitor of Metalloproteinase and homocysteine‐metabolizing enzymes Post myocardial Infarction in Mice.

Abstract

Myocardial infarction (MI) results in significant metabolic derangement in myocardium. Homocysteine (Hcy), a non‐protein amino acid, was generated during nucleic acid methylation and methionine de‐methylation. However, the role of Hcy metabolism in derangement of in myocardial injury after MI is not known. Folic acid (FA) decreased Hcy levels by remethylating the Hcy to methionine, by 5‐methylene tetrahydrofolate reductase (5‐MTHFR). The derangement in Hcy metabolism/clearance led to hyperhomocysteinemia (HHcy) and cardiovascular dysfunction; and MI resulted in significant metabolic derangement. The fraction shortening (FS) was 58% (sham) and 27% (MI). FA supplementation resulted in significantly preserving FS to 41%. The ejection fraction was closely paralleled the FS. The calcium transients and contractile function were found to be lower after MI but markedly improved in MI hearts with FA supplementation. The levels of TIMP were decreased significantly in MI hearts. Interesting, the decrease in TIMP expression in MI was mitigated after FA treatment. The decreased levels of cystathionine beta synthase (CBS), cystathionine gamma lyase (CSE), and 5‐MTHFR in MI hearts were ameliorated by FA‐treatment. The present study suggests that FA supplementation results in significant preservation of myocardial function in mouse heart after MI, in part, by homocysteine metabolic pathway.