The Inflammatory Impact of Cytomegalovirus on the Microvasculature, and its Cooperation with Other Cardiovascular Risk Factors
Inflammation is a key player in the pathogenesis of cardiovascular disease. In the case of several cardiovascular risk factors, including hypercholesterolemia, clinical signs of disease are preceded by the development of an inflammatory phenotype in the microvasculature, which may promote a low-grade systemic inflammation rendering tissues more susceptible to injurious stimuli or other risk factors. Recent epidemiological studies have revealed that infectious agents, for example cytomegalovirus (CMV), may contribute to cardiovascular disease. CMV is a b -herpesvirus that has been identified in atherosclerotic lesions, and accelerates disease progression in hyperlipidemic animals. CMV induces an inflammatory phenotype in isolated cells. Our preliminary data suggests that CMV also induces endothelial dysfunction in arterioles in vivo, and exacerbates hypercholesterolemia-induced blood cell recruitment in postcapillary venules. Therefore our focus is to investigate the underlying mechanisms involved in the microvascular responses to CMV, and its cooperation with hypercholesterolemia in the generation of a pro-inflammatory phenotype.

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In a normocholesterolemic mouse, cytomegalovirus infection leads to an impaired vasodilation response to acetylcholine in arterioles, however venules do not show obvious signs of inflammation. In contrast, when mice are placed on a cholesterol-enriched diet, arteriolar function is impaired further, and leukocyte recruitment occurs in the venules. The underlying mechanisms are under investigation.