Herpesvirus infection enhances cholesterol and cholesteryl ester accumulation in cultured arterial smooth muscle cells.
In our previous experiments, atherosclerosis similar to that in humans was reproducibly induced in both normocholesterolemic and hypercholesterolemic specific-pathogen-free (SPF) chickens by infection with Marek's disease herpesvirus (MDV). In contrast, uninfected chickens fed either relatively cholesterol-poor or cholesterol-supplemented diets did not develop this arterial disease. In experiments reported here, the hypothesis that infection of arterial smooth muscle cells (SMCs) with MDV would enhance lipid accumulation in these cells was tested. The number of MDV-infected SMCs with lipid stained with oil red O was assessed, and the lipid content of these cells was quantitated chemically by chromatographic and fluorometric analyses. These data were compared to those of uninfected control cells and, in the case of chemical analyses, were also compared to SMCs infected with a second avian herpesvirus, turkey herpesvirus (HVT). Results indicate the following: 1) The percentage of MDV-infected SMCs containing stainable lipid was significantly greater than the percentage of uninfected SMCs; 2) Increased total lipid accumulation was observed in MDV-infected SMC, particularly cholesterol (CH) and cholesteryl esters (CEs), as compared with uninfected or HVT-infected cells; 3) The types of CEs and nonesterified fatty acids (NEFA) accumulating in MDV-infected cells (particularly saturated types of CEs and NEFAs) were significantly different than those in uninfected or HVT-infected SMCs. These qualitative and quantitative differences in lipid content between infected and uninfected SMCs suggest that infection with MDV results in altered intracellular lipid metabolism. Results support the hypothesis that lipid accumulation in arteries of normocholesterolemic chickens may result from MDV infection acting at the cellular level to induce lipid accumulation that resembles that in human atheroarteriosclerosis.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002478:Cells, Cultured; D002645:Chickens; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D002788:Cholesterol Esters / Q000032:analysis / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000378:metabolism; D006566:Herpesviridae Infections / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D008380:Marek Disease / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000032:analysis / Q000378:metabolism*; D014422:Turkeys
D002788:Cholesterol Esters; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D002784:Cholesterol