Abstract 341: Expression of Leukocyte CD39 in Acute Coronary Syndrome
Background CD39 (ENTPD-1) is a membrane-spanning ectonucleotidase that is responsible for the phosphohydrolysis of ATP to ADP and ADP to AMP. As increased myocardial infarct sizes have been reported in murine CD39 knockout models when compared with controls, we hypothesized that CD39 might be expressed as part of the myocardial injury/repair response. CD39 levels have not been heretofore described in humans with acute coronary syndrome (ACS).
Objectives To measure CD39 mRNA and protein levels in human study subjects with ACS compared with healthy controls.
Methods Healthy subjects (n=24), defined as having no history of coronary or peripheral arterial disease, and subjects with ACS (n=13) were enrolled in the study. Blood was collected via venupuncture for healthy controls or at the time of cardiac catheterization for ACS subjects. Plasma and leukocytes were isolated from blood, and soluble CD39 protein from leukocytes was measured using ELISA. mRNA was extracted from leukocytes, and qPCR was used to measure differences in leukocyte CD39 mRNA. Mass spec was used to assess plasma ATP, ADP, AMP, and adenosine levels.
Findings Increased CD39 mRNA expression was found in subjects with ACS when compared with healthy controls (2.39 vs. 1.66, p=0.021). There was a trend towards increased leukocyte CD39 protein concentrations in ACS patients (n=5) compared to controls (n=9) (7.50 ng/ml vs. 2.64 ng/ml, p=0.057) when measured by ELISA. There was a trend toward increased levels of soluble plasma CD39 levels in ACS patients (n=12) when compared with controls (n=24) (2.39 ng/ml vs. 1.67 ng/ml, p=0.59) when measured by ELISA. ACS patients (n=11) were found to have higher levels of circulating ADP as assessed by Mass spec when compared with healthy controls (n=17), 2.02 vs. 0.67, p=0.03. Leukocyte CD39 levels positively correlated with ATP (r2 =.231) and ADP (r2=.155) levels (n=10).
Conclusions This is the first report of increased CD39 gene expression in patients with ACS, when compared with healthy controls without known coronary disease. A trend toward increased plasma and leukocyte CD39 protein expression was present in those with ACS when compared with controls. CD39 could serve as a modulator of vascular homeostasis in ACS.
- © 2013 by American Heart Association, Inc.