Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease.
Folic acid (FA) is a member of the B-vitamin family with cardiovascular roles in homocysteine regulation and endothelial nitric oxide synthase (eNOS) activity. Its interaction with eNOS is thought to be due to the enhancement of tetrahydrobiopterin bioavailability, helping maintain eNOS in its coupled state to favor the generation of nitric oxide rather than oxygen free radicals. FA also plays a role in the prevention of several cardiac and noncardiac malformations, has potent direct antioxidant and antithrombotic effects, and can interfere with the production of the endothelial-derived hyperpolarizing factor. These multiple mechanisms of action have led to studies regarding the therapeutic potential of FA in cardiovascular disease. To date, studies have demonstrated that FA ameliorates endothelial dysfunction and nitrate tolerance and can improve pathological features of atherosclerosis. These effects appear to be homocysteine independent but rather related to their role in eNOS function. Given the growing evidence that nitric oxide synthase uncoupling plays a major role in many cardiovascular disorders, the potential of exogenous FA as an inexpensive and safe oral therapy is intriguing and is stimulating ongoing investigations.
Moens
An L
AL
Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. an.moens@uza.be
Vrints
Christiaan J
CJ
Claeys
Marc J
MJ
Timmermans
Jean-Pierre
JP
Champion
Hunter C
HC
Kass
David A
DA
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006330:Heart Defects, Congenital / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism
D002317:Cardiovascular Agents; D006710:Homocysteine; D009569:Nitric Oxide; D005492:Folic Acid; D052250:Nitric Oxide Synthase Type III