The Role of Cystathionine Gamma Lyase and Endothelial Nitric Oxide Synthase for Cardiovascular Homeostasis

Abstract

Nitric oxide (NO) and hydrogen sulfide (H2S) are two important vasoactive gasotransmitters. Both NO and H2S are essential in the genesis, development, repair and remodeling of blood vessels. They also have a cardio‐protective role that stems from their ability to regulate vasodilation, blood pressure and and the growth of new blood vessels. Genetic deficiency of either endothelial NO synthase (eNOS) or Cystathionine γ‐lyase (CSE, one of the genes implicated in H2S synthesis) has detrimental effects on tissue vascularization and vascular repair against shear forces and atherosclerotic changes. While the deletion of either gene alone has been previously studied; the effects of genetic deficiency of both genes together in the same animal has not been previously evaluated. In this study, we report that when both genes are deleted severe cardiovascular pathological changes emerge. Cardiac ejection fraction (EF) and fraction shortening (FS) measured on 2D/M mode echocardiogram performed on homozygous eNOS/CSE double knockout mice was severely diminished compared to that of homozygous CSE null/heterozygous eNOS knockout mice. H&E stained sections of the aorta showed significant changes with irregular, eosinophilic and less defined elastic laminae with loss of refractility and edematous tunica media with pauci‐cellularity and hypochromatic nuclei. These data are the first to reveal a critical relationship between eNOS and CSE expression for basal cardiac function and tissue histological organization.Support or Funding InformationThis work supported by HL113303