Therapeutic potential of tetrahydrobiopterin for treating vascular and cardiac disease.
Tetrahydrobiopterin is the reduced unconjugated pterin that serves as an essential cofactor for the normal enzymatic function of the aromatic amino acid hydroxylases and for the nitric oxide synthases (NOS). Its role in the latter biochemistry is being increasing appreciated, as depletion or oxidation of BH4 results in a condition of NOS uncoupling, resulting in a nitroso-oxidative imbalance. Recent experimental studies support an important pathophysiologic role of BH4 deficiency as well as the therapeutic potential of BH4 repletion for hypertension, endothelial dysfunction, atherosclerosis, diabetes, cardiac hypertrophic remodeling, and heart failure. In addition to BH4, studies are also examining the potential role of folic acid therapy, because folic acid can enhance BH4 levels and the NOS coupling state. This review summarizes these recent studies focusing on the biochemistry and pharmacology of BH4 and its potential role for treating cardiovascular disease.
Moens
An L
AL
Department of Cardiology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Kass
David A
DA
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism
D002317:Cardiovascular Agents; D001708:Biopterins; D005492:Folic Acid; D019001:Nitric Oxide Synthase; C003402:sapropterin