Genetic deletion of CD38 confers post-ischemic myocardial protection through preserved pyridine nucleotides

Journal of Molecular and Cellular Cardiology
James BoslettJay L Zweier

Abstract

Following the onset of ischemia/reperfusion (I/R), CD38 activation occurs and is associated with depletion of NAD(P)(H) in the heart as well as myocardial injury and endothelial dysfunction. Studies with pharmacological inhibitors suggest that the NADP+-hydrolyzing ability of CD38 can deplete the NAD(P)(H) pools. However, there is a need for more specific studies on the importance of CD38 and its role in the process of endothelial dysfunction and myocardial injury in the post-ischemic heart. Therefore, experiments were performed in hearts of mice with global gene knockout of CD38. Isolated perfused CD38-/- and wild type (WT) mouse hearts were studied to determine the link between CD38 activation, the levels of NADP(H), endothelial dysfunction, and myocardial injury after I/R. Genetic deletion of CD38 preserves the myocardial and endothelial NADP(H) pools compared to WT. Whole heart BH4 levels in CD38-/- hearts were also preserved. Post-ischemic levels of cGMP were greatly depleted in WT hearts, but preserved to near baseline levels in CD38-/- hearts. The preservation of these metabolite pools in CD38-/- hearts was accompanied by near full recovery of NOS-dependent coronary flow, while in WT hearts, severe impairment of endothel...Continue Reading

Citations

Jan 13, 2019·The Journal of Pharmacology and Experimental Therapeutics·James BoslettJay L Zweier
May 31, 2020·Cardiovascular Drugs and Therapy·Wanyun ZuoQiming Liu
Jul 23, 2020·Nature Metabolism·Elena KatsyubaJohan Auwerx
Oct 11, 2020·Cells·Déborah Cardoso, Antoine Muchir
Nov 18, 2020·Nature Metabolism·Claudia C S ChiniEduardo N Chini
Mar 9, 2019·Free Radical Biology & Medicine·Hong YuRonald J Korthuis
Nov 30, 2021·Circulation·Mahmoud AbdellatifGuido Kroemer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.