Chlamydia pneumoniae infection of human endothelial cells induces proliferation of smooth muscle cells via an endothelial cell-derived soluble factor(s)

An association of Chlamydia pneumoniae with atherosclerosis and coronary he art disease has been determined epidemiologically and by the detection of C . pneumoniae organisms in atherosclerotic lesions in both humans and animal models of atherosclerosis. Previously, it has been shown that C. pneumonia e is capable of replicating in cell types found within atheromatous lesions , viz., endothelial cells, smooth muscle cells (SMC), and macrophages, yet the role of C. pneumoniae in the pathogenesis of atherosclerosis has not be en determined. Since intimal thickening is a hallmark of atherosclerosis, w e investigated whether C. pneumoniae infection of human umbilical vein endo thelial cells (HUVEC) could induce the expression of a soluble factor(s) wi th mitogenic potential for SMC by using [H-3]thymidine incorporation and di rect cell counting. Conditioned medium harvested from HUVEC infected with C . pneumoniae stimulated SMC replication in a time- and dose-dependent fashi on. Infection studies using various multiplicities of infection (MOIs) rang ing 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, respective ly. To determine whether viable C. pneumoniae was required for production o f the soluble factor(s), HUVEC were infected with heat-inactivated C. pneum oniae or with viable organisms in the presence of chloramphenicol. Both tre atments produced stimulation indices similar to those for live C. pneumonia e in the absence of chloramphenicol (P > 0.05), indicating that the factor( s) was produced by HUVEC and not by C. pneumoniae and that signal transduct ion events following chlamydia endocytosis may be important in the producti on of a soluble factor(s). The ability of C. pneumoniae to elicit an endoth elial cell-derived soluble factor(s) that stimulates SMC proliferation may be important in the pathogenesis of atherosclerosis.