Human atheromatoma have ben shown to originate as monoclonal foci ofproliferating transformed arterial smooth muscle cells (SMC). Benditt postulated that transforming agents may be atherogenic. Two carcinogenic hydrocarbons and one transformig avian herpesvirus, Marek's disease virus (MDV), have been found to be atherogenic in chickens, even on a normal or low cholesterol diet. Chicken arterial SMC in culture, when infected with MDV, undergo a lipid metabolic imbalance that quantitatively and qualitatively resembles that of human atherosclerotic arteries. Spontaneous MDV-induced epizootics of chicken lymphomatosis have been accompanied by a significant increase in the incidence and severity of coronary artery sclerosis in infeted flocks. A human herpes virus, cytomegalovirus (CMV), has been detected by innumofluorescence in more than 25% of arterial smooth muscle cell cultures derived from arteriosclerotic and grossly uninvolved arterial specimens. all from patients with advanced arteriosclerotic disease, from this medical center. An extensive sero-epidemiological survey of hundreds of patients undergoing arteriosclerotic vascular surgery, and paried controls with high plasma low density lipoprotein cholessterol but no evidence of heart disease, has further implicated CMV in the pathogenesis of atherosclerosis. We have demonstrated that CMV strain AD-169 infects and replicates very slowly over a peroid of months in cultured human umbilical cord arterial SMC (10). We plan to test different strain of human CMV, including one transforming strain, and one candidate vaccine strain, for ability to infect and grow in human arterial SMC cultures. We will study infected and control cultures for evidence of cholesterol metabolic imbalance resembling that of human atherosclerotic arteries, and of chicken arterial SMC infected with MDV.
| Datta, S K; Tumilowicz, J J; Trentin, J J (1993) Lysis of human arterial smooth muscle cells infected with herpesviridae by peripheral blood mononuclear cells: implications for atherosclerosis. Viral Immunol 6:153-60 |
