Abstract 267: CD93: A Novel Myocardial Infarction- Associated Protein with Glucose Regulatory Properties in Humans and Mice
Introduction: Coronary artery disease (CAD) is a complex disorder involving metabolic, and inflammatory mechanisms. Previously, we have shown that plasma levels of soluble CD93 (sCD93) are inversely associated with CAD events in women. Yet, little is known about the role of sCD93 in disease progression or its association with metabolic pathways.
Hypothesis: In this study we asked whether plasma levels of sCD93 could be associated with type 2 diabetes (T2D), a major risk factor for CAD. In parallel, we investigated CD93-mediated effects in metabolism and inflammation using a newly established mouse model.
Methods: Soluble CD93 was measured by Mesoscale® in plasma of subjects from the IMPROVE cohort, (3371 subjects). IMPROVE is a prospective, multicentre, longitudinal, observational study with subjects presenting at least 3 established CVD risk factors but no clinical coronary artery disease at baseline. T2D was defined clinically or by blood fasting glucose ≥7mmol/L. Detailed ultrasound carotid intima-media thickness (cIMT) phenotypes at baseline, 15 and 30 months were assessed.
In parallel, cd93 heterozygous deficient mice were established by KOMP repository using C57Bl/6N ES cells (CD93low). These mice were then used in a T2D model by giving a high fat diet (21% fat 0.2% cholesterol) or crossed into C57Bl6/N.ApoE deficient mice in order to establish a murine atherosclerosis model.
Results: Soluble CD93 levels presented significantly lower in subjects with T2D compared to those without (n= 901 vs 2470; mean ± sd = 156.6±40.0ng/ml vs 164.1±44.8ng/ml, respectively; p<0.0001). However, no association between sCD93 cIMT was observed. In line with this, analysis of ApoE-/-CD93low revealed no changes in atherosclerotic lesion development compared to ApoE-/-CD93 sufficient littermates. Nevertheless, in consensus with the clinical findings, CD93low mice showed impaired glucose clearance and reduced insulin sensitivity compared to littermate controls in the T2D model.
Conclusion: Levels of sCD93 were inversely correlated with T2D in a CAD high-risk cohort, furthermore the mouse T2D models indicates CD93 as a glucose-regulating molecule. However, it remains to be determined how CD93 is involved in glucose regulation.
Author Disclosures: A. Bäcklund: None. R. Strawbridge: None. H. Jin: None. P. Tsikrika: None. A. Silveira: None. D.F.J. Ketelhuth: None. P. Eriksson: None. L. Maegdefessel: None. A. Hamsten: None.
- © 2015 by American Heart Association, Inc.