CD38 deficient mice are not protected from atherosclerosis

Abstract

CD38 is a multifunctional enzyme implicated in chemotaxis of myeloid cells and lymphocyte activation, but also expressed by resident cells such as endothelial and smooth muscle cells. CD38 is important for host defense against microbes. However, CD38's role in the pathogenesis of atherosclerosis is controversial with seemingly conflicting results reported so far. To clarify the discrepancy of current literature on the effect of CD38 ablation on atherosclerosis development, we implanted a shear stress modifier around the right carotid artery in CD38−/− and WT mice. Hypercholesterolemia was induced by human gain-of-function PCSK9 (D374Y), introduced using AAV vector (serotype 9), combined with an atherogenic diet for a total of 9 weeks. Atherosclerosis was assessed at the aortic root, aortic arch and the right carotid artery. The findings can be summarized as follows: i) CD38−/− and WT mice had a similar atherosclerotic burden in all three locations, ii) No significant differences in monocyte infiltration or macrophage content could be seen in the plaques, and iii) The amount of collagen deposition in the plaques were also similar between CD38−/− and WT mice. In conclusion, our data suggest that CD38−/− mice are neither protected against nor prone to atherosclerosis compared to WT mice.