Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice.
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.
Qipshidze
Natia
N
Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Tyagi
Neetu
N
Sen
Utpal
U
Givvimani
Srikanth
S
Metreveli
Naira
N
Lominadze
David
D
Tyagi
Suresh C
SC
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
D006397:Hematinics; D019714:Tissue Inhibitor of Metalloproteinases; D006710:Homocysteine; D005492:Folic Acid; D020782:Matrix Metalloproteinases
Diabetes. 2009 Aug;58(8):1921-8
19491213
Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H890-7
18567713
Br J Clin Pharmacol. 2002 Feb;53(2):189-92
11851643
Nat Rev Mol Cell Biol. 2007 Mar;8(3):221-33
17318226
Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H1858-64
15937097
Arch Physiol Biochem. 2010 May;116(2):63-72
20230216
Am J Hypertens. 2002 Feb;15(2 Pt 1):157-63
11863251
Atherosclerosis. 1995 Jul;116(1):43-57
7488332
Clin Exp Hypertens. 2002 Jul;24(5):397-406
12109779
J Am Coll Cardiol. 1999 Dec;34(7):2002-6
10588216
Am J Cardiol. 1992 Oct 8;70(10):20C-26C
1414891
Br J Nutr. 1974 Sep;32(2):457-69
4417592
J Biol Chem. 1999 Apr 16;274(16):10846-51
10196161
J Clin Invest. 1994 Dec;94(6):2493-503
7989608
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1869-76
17604325
JAMA. 1995 Oct 4;274(13):1049-57
7563456
Life Sci. 1997;61(13):1205-15
9324062
Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1229-35
12775562
Biomed Environ Sci. 2008 Dec;21(6):514-20
19263808
Circulation. 1988 Jul;78(1):186-201
2968197
J Cell Biochem. 2001;80(4):512-21
11169735
Life Sci. 2007 Jan 23;80(7):638-43
17118406
Circulation. 2006 Sep 12;114(11):1193-201
16940192
J Clin Invest. 2000 Jul;106(1):55-62
10880048
J Am Coll Cardiol. 1988 Jan;11(1):12-9
3335689
Am J Physiol Heart Circ Physiol. 2000 Sep;279(3):H970-5
10993757
Neurochem Int. 2008 Dec;53(6-8):214-9
18725259
Br J Nutr. 2001 Dec;86(6):637-9
11749673
Blood. 1998 Mar 15;91(6):2015-8
9490685
Circulation. 1990 Apr;81(4):1161-72
2138525
Brain Res. 2008 Jul 24;1221:147-53
18547546
Biochem Biophys Res Commun. 1984 Jan 13;118(1):14-9
6696751
Am J Cardiol. 1978 Jun;41(7):1127-32
665522
Ann Intern Med. 1999 Sep 7;131(5):363-75
10475890
J Clin Invest. 1998 Mar 15;101(6):1478-87
9502791
Am J Physiol Cell Physiol. 2009 Apr;296(4):C840-7
19193866
Circulation. 1993 Dec;88(6):2565-74
8080490
J Lab Clin Med. 2003 Nov;142(5):288-97
14647032
Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):1196-202
11451751
JAMA. 2010 Apr 28;303(16):1603-9
20424250
Circ Res. 2010 Mar 5;106(4):796-808
20056917
J Cell Biochem. 2006 Aug 1;98(5):1150-62
16514665
Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H461-8
15650153
Circulation. 1979 Dec;60(7):1532-8
498481
J Cell Biochem. 1997 Jun 1;65(3):388-94
9138094
Nutr Res. 2009 Nov;29(11):794-801
19932868
Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H372-8
17993597
J Nutr Biochem. 2004 Feb;15(2):64-79
14972346
Nat Protoc. 2008;3(9):1422-34
18772869
Circulation. 1998 Jan 27;97(3):237-41
9462523
Circulation. 2008 Apr 8;117(14):1810-9
18362233