title: Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice.
abstract: Myocardial infarction (MI) results in significant metabolic derangement, causing accumulation of metabolic by product, such as homocysteine (Hcy). Hcy is a nonprotein amino acid generated during nucleic acid methylation and demethylation of methionine. Folic acid (FA) decreases Hcy levels by remethylating the Hcy to methionine, by 5-methylene tetrahydrofolate reductase (5-MTHFR). Although clinical trials were inconclusive regarding the role of Hcy in MI, in animal models, the levels of 5-MTHFR were decreased, and FA mitigated the MI injury. We hypothesized that FA mitigated MI-induced injury, in part, by mitigating cardiac remodeling during chronic heart failure. Thus, MI was induced in 12-wk-old male C57BL/J mice by ligating the left anterior descending artery, and FA (0.03 g/l in drinking water) was administered for 4 wk after the surgery. Cardiac function was assessed by echocardiography and by a Millar pressure-volume catheter. The levels of Hcy-metabolizing enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 5-MTHFR, were estimated by Western blot analyses. The results suggest that FA administered post-MI significantly improved cardiac ejection fraction and induced tissue inhibitor of metalloproteinase, CBS, CSE, and 5-MTHFR. We showed that FA supplementation resulted in significant improvement of myocardial function after MI. The study eluted the importance of homocysteine (Hcy) metabolism and FA supplementation in cardiovascular disease.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Natia
authors.initials: N
authors.lastname: Qipshidze
authors.forename: Neetu
authors.initials: N
authors.lastname: Tyagi
authors.forename: Utpal
authors.initials: U
authors.lastname: Sen
authors.forename: Srikanth
authors.initials: S
authors.lastname: Givvimani
authors.forename: Naira
authors.initials: N
authors.lastname: Metreveli
authors.forename: David
authors.initials: D
authors.lastname: Lominadze
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006397:Hematinics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006710:Homocysteine / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D006397:Hematinics; D019714:Tissue Inhibitor of Metalloproteinases; D006710:Homocysteine; D005492:Folic Acid; D020782:Matrix Metalloproteinases
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