Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin

An L. Moens, Rinrada Kietadisorn, Judy Y. Lin, David A Kass

Research output: Contribution to journalArticle

Abstract

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".

Original languageEnglish (US)
Pages (from-to)559-563
Number of pages5
JournalJournal of Molecular and Cellular Cardiology
Volume51
Issue number4
DOIs
StatePublished - Oct 2011

Fingerprint

Nitric Oxide Synthase
Biological Availability
Reactive Nitrogen Species
Aromatic Amino Acids
Phenylketonurias
Nitric Oxide Synthase Type III
Therapeutic Uses
Mixed Function Oxygenases
Reperfusion Injury
Hypertrophy
Reactive Oxygen Species
Protein Isoforms
Heart Failure
Antioxidants
Hypertension
Pharmaceutical Preparations
sapropterin
Therapeutics
Body Remains

Keywords

  • Endothelial dysfunction
  • ENOS-uncoupling
  • Myocardial dysfunction
  • Sapropterin
  • Tetrahydrobiopterin
  • Ventricular remodeling and heart failure

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin. / Moens, An L.; Kietadisorn, Rinrada; Lin, Judy Y.; Kass, David A.

In: Journal of Molecular and Cellular Cardiology, Vol. 51, No. 4, 10.2011, p. 559-563.

Research output: Contribution to journalArticle

Moens, An L. ; Kietadisorn, Rinrada ; Lin, Judy Y. ; Kass, David A. / Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin. In: Journal of Molecular and Cellular Cardiology. 2011 ; Vol. 51, No. 4. pp. 559-563.
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