Herpes virus infection of endothelium: new insights into atherosclerosis.
Several pieces of evidence suggest that vascular endothelium may be a site of latent herpetic viral infection, and that activation of such infection might cause or aggravate atherosclerosis. The present studies which utilized HSV-1 infection of cultured endothelial monolayers, provide insights into two phenomena seemingly relevant in considerations of atherosclerosis. Thus, mechanisms are reported by which infected endothelium may be damaged by marginated inflammatory cells, and be transformed from an anticoagulant to a procoagulant tissue. First, granulocytes are attracted to, and avidly bind, endothelium infected for very brief periods. This interaction is associated with denudation of intact cells as well as actual cytolysis through release of PMN proteases and toxic oxygen species. Second, several potentially additive abnormalities of HSV-infected endothelium would seem to foster coagulation. These include: a) its loss of surface heparans and thrombomodulin; b) its inability to synthesize prostacyclin with associated incapacity to deter platelet adhesion; c) its disordered membrane lipid conformation which is likely associated with excessive surface thrombin generation; and d) its unique ability to generate and release tissue factor. We speculate that mechanical abrasion may reactivate latent herpes (HSV or CMV) infection in endothelial cells particularly those exposed to high shear forces--for instance, at vessel bifurcations. This may underlie the endothelial damage, clotting and atheroma formation commonly found at these sites.
Jacob
H S
HS
Department of Medicine, University of Minnesota Medical School, Minneapolis.
Visser
M
M
Key
N S
NS
Goodman
J L
JL
Moldow
C F
CF
Vercellotti
G M
GM
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology*; D001777:Blood Coagulation; D002478:Cells, Cultured; D004730:Endothelium, Vascular; D006561:Herpes Simplex / Q000150:complications; D006566:Herpesviridae Infections / Q000150:complications*; D006801:Humans; D014657:Vasculitis / Q000150:complications