An association of
Chlamydia pneumoniaewith atherosclerosis and coronary heart disease has been determined epidemiologically and by the detection of C. pneumoniaeorganisms in atherosclerotic lesions in both humans and animal models of atherosclerosis. Previously, it has been shown that C. pneumoniaeis capable of replicating in cell types found within atheromatous lesions, viz., endothelial cells, smooth muscle cells (SMC), and macrophages, yet the role of C. pneumoniaein the pathogenesis of atherosclerosis has not been determined. Since intimal thickening is a hallmark of atherosclerosis, we investigated whether C. pneumoniaeinfection of human umbilical vein endothelial cells (HUVEC) could induce the expression of a soluble factor(s) with mitogenic potential for SMC by using [ 3 H]thymidine incorporation and direct cell counting. Conditioned medium harvested from HUVEC infected with C. pneumoniaestimulated SMC replication in a time- and dose-dependent fashion. Infection studies using various multiplicities of infection (MOIs) ranging from 0.001 to 1 demonstrated a dose-dependent production of the soluble factor(s). At an MOI of 1, SMC stimulation indices were 8.4 ( P< 0.01) and 12.2 ( P< 0.01) for conditioned media harvested at 24 and 48 h, respectively. To determine whether viable C. pneumoniaewas required for production of the soluble factor(s), HUVEC were infected with heat-inactivated C. pneumoniaeor with viable organisms in the presence of chloramphenicol. Both treatments produced stimulation indices similar to those for live C. pneumoniaein the absence of chloramphenicol ( P> 0.05), indicating that the factor(s) was produced by HUVEC and not by C. pneumoniaeand that signal transduction events following chlamydia endocytosis may be important in the production of a soluble factor(s). The ability of C. pneumoniaeto elicit an endothelial cell-derived soluble factor(s) that stimulates SMC proliferation may be important in the pathogenesis of atherosclerosis.