Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury

Author:

Chuaiphichai Surawee1ORCID,Chu Sandy M.1,Carnicer Ricardo1,Kelly Matthew1,Bendall Jenifer K.1,Simon Jillian N.2ORCID,Douglas Gillian1,Crabtree Mark J.3,Casadei Barbara1ORCID,Channon Keith M.1ORCID

Affiliation:

1. Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom

2. Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States

3. Department of Biochemical Sciences, School of Bioscience and Medicine, University of Surrey, Guildford, United Kingdom

Abstract

We demonstrate a critical role for endothelial cell Gch1/BH4 biosynthesis in coronary vascular function and cardiac function. Loss of cardiac endothelial cell BH4 leads to coronary vascular dysfunction, reduced functional recovery, and increased myocardial infarct size following ischemia/reperfusion injury. Targeting endothelial cell Gch1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of cardiac dysfunction, ischemia injury, and heart failure.

Funder

National Institute for Health Research

British Heart Foundation

Wellcome Trust

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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