Cytomegalovirus promotes arteriolar dysfunction and exacerbates inflammatory responses to hypercholesterolemia

Abstract

Cytomegalovirus (CMV), which infects >60% of humans, has been identified in atherosclerotic lesions, and accelerates plaque development in atherosclerosis-prone mice. However the impact of CMV on the microvasculature in the absence or presence of elevated cholesterol levels is unknown. The objective of this study was to determine if CMV promotes inflammation in arterioles and venules, and if CMV synergizes with hypercholesterolemia to exaggerate these responses. Intravital microscopy was used to assess arteriolar vasodilation and venular leukocyte adhesion in mice infected with mock inoculum or CMV for 4, 6, 9 or 12wk, and fed normal (ND) or high cholesterol (HC) diet for the final 4wk. CMV-ND mice exhibited a progressive impairment of endothelium-dependent vasodilation to acetylcholine when compared to mock-ND. No inflammation was evident in venules of CMV-ND mice. HC did not alter responses in arterioles or venules of the mock group. However CMV-HC led to a significant arteriolar dysfunction at all time-points examined. Leukocyte adhesion in CMV-HC venules was significantly elevated between 6 and 12wks post-infection (versus mock-HC), peaking at 9wk. These findings reveal a site-specific pro-inflammatory influence of CMV on the microvasculature, and suggest that CMV infection enhances the susceptibility of the microvasculature to inflammation caused by hypercholesterolemia. (Grant: AHA 0565285B)