Membrane-Bound Enzyme Linked to Plaque Formation in Mouse Atherosclerosis Model

Cardiac disease researchers working with a mouse model of atherosclerosis have found that that a specific membrane bound enzyme has the potential to inhibit build-up of plaque and reduce risk of heart attack or stroke.

Investigators at the University of Michigan (Ann Arbor, USA) worked with the apolipoprotein E-deficient (ApoE-deficient) mouse model of atherosclerosis to examine the role of the enzyme CD39 (ectonucleotide tri(di)phosphohydrolase-1 or ENTPD1) in the process of plaque formation. This enzyme metabolizes locally released, intravascular ATP and ADP, thereby eliminating these pro-thrombotic and pro-inflammatory signaling molecules.

The investigators reported in the June 29, 2015, online edition of the Journal of Clinical Investigation that when animals fed a high-fat diet were compared, it was seen that ApoE-deficient mice that also lacked CD39 had a plaque burden that was markedly increased along with circulating markers of platelet activation. CD39 was prominently expressed in stable blood flow regions and was diminished in areas subjected to disturbed flow. Thus, CD39 activation followed the pattern of plaque formation.

In mice, disturbed blood flow as the result of partial carotid artery ligation rapidly suppressed endothelial CD39 expression. Moreover, unidirectional laminar shear stress induced protective CD39 expression in human endothelial cells.

“Better lifestyles and improved treatments have slowed the rates of death from atherosclerosis, but if CD39 proves to be as critical a factor in humans as in mice, it would be a major step forward in understanding heart disease,” said senior author Dr. David Pinsky, professor of cardiology at the University of Michigan.

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