TY - JOUR
T1 - Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin
AU - Moens, An L.
AU - Kietadisorn, Rinrada
AU - Lin, Judy Y.
AU - Kass, David
N1 - Funding Information:
There are no conflicts of interest. This review is supported by Dutch Heart Society (Subsidiebeurs-2009) and Dutch Government (ZONMW/VIDI)-(ALM) and by NHLBI-HL-089297 and Fondation Leducq (DAK).
PY - 2011/10
Y1 - 2011/10
N2 - Tetrahydrobiopterin (BH 4) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. It also has a protective role in the cell as an antioxidant and scavenger of reactive nitrogen and oxygen species. Experimental studies in humans and animals demonstrate that decreased BH 4-bioavailability, with subsequent uncoupling of endothelial NOS (eNOS) plays an important role in the pathogenesis of endothelial dysfunction, hypertension, ischemia-reperfusion injury, and pathologic cardiac remodeling. Synthetic BH 4 is clinically approved for the treatment of phenylketonuria, and experimental studies support its capacity for ameliorating cardiovascular pathophysiologies. To date, however, the translation of these studies to human patients remains limited, and early results have been mixed. In this review, we discuss the pathophysiologic role of decreased BH 4 bioavailability, molecular mechanisms regulating its metabolism, and its potential therapeutic use as well as pitfalls as an NOS-modulating drug. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure".
AB - Tetrahydrobiopterin (BH 4) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. It also has a protective role in the cell as an antioxidant and scavenger of reactive nitrogen and oxygen species. Experimental studies in humans and animals demonstrate that decreased BH 4-bioavailability, with subsequent uncoupling of endothelial NOS (eNOS) plays an important role in the pathogenesis of endothelial dysfunction, hypertension, ischemia-reperfusion injury, and pathologic cardiac remodeling. Synthetic BH 4 is clinically approved for the treatment of phenylketonuria, and experimental studies support its capacity for ameliorating cardiovascular pathophysiologies. To date, however, the translation of these studies to human patients remains limited, and early results have been mixed. In this review, we discuss the pathophysiologic role of decreased BH 4 bioavailability, molecular mechanisms regulating its metabolism, and its potential therapeutic use as well as pitfalls as an NOS-modulating drug. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure".
KW - ENOS-uncoupling
KW - Endothelial dysfunction
KW - Myocardial dysfunction
KW - Sapropterin
KW - Tetrahydrobiopterin
KW - Ventricular remodeling and heart failure
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U2 - 10.1016/j.yjmcc.2011.03.009
DO - 10.1016/j.yjmcc.2011.03.009
M3 - Review article
C2 - 21458460
AN - SCOPUS:79960803194
SN - 0022-2828
VL - 51
SP - 559
EP - 563
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 4
ER -