Warner-Lambert/Parke-Davis Award Lecture. Viral pathogenesis of atherosclerosis. Impact of molecular mimicry and viral genes.
Human atherogenesis is a pleiotropic process with an undefined cause. Several pathologic factors have been linked to the disease process, including arterial injury or activation of the endothelium, which may injury or activation of the endothelium, which may initiate proatherosclerotic events in the vessel wall. Atherosclerotic lesions are characterized, in part, by the presence of activated immune cells, abnormal cell proliferation, and altered cholesterol metabolism. These activated immunocompetent cells in plaques produce vasoactive mediators that can alter homeostasis and may promote the arteriopathy. Both molecular and structural evidence is presented that herpesviruses, by way of induction of altered gene function and cellular cholesterol metabolism, coupled with their ability to activate coagulation and a monocyte receptor on the infected endothelium, are involved in major pathogenic events associated with atherosclerosis and thrombosis. Work from the author's laboratory, as well as from other research groups, have shown that avian and human herpesviruses act specifically to induce alterations to the surface and inner layers of the blood vessel wall that may predispose to atherosclerosis and its attendant clinical complications.
Hajjar
D P
DP
Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology; D001777:Blood Coagulation; D001808:Blood Vessels / Q000166:cytology / Q000382:microbiology; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008967:Molecular Biology; D013927:Thrombosis / Q000209:etiology; D014777:Virus Diseases / Q000150:complications*
D016207:Cytokines; D002784:Cholesterol