Chlamydia pneumoniae
Infection of Human Endothelial Cells Induces Proliferation of Smooth Muscle Cells via an Endothelial Cell-Derived Soluble Factor(s)
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abstract
ABSTRACT
An association of
Chlamydia pneumoniae
with atherosclerosis and coronary heart 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. pneumoniae
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 been determined. Since intimal thickening is a hallmark of atherosclerosis, we investigated whether
C. pneumoniae
infection 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. pneumoniae
stimulated 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. pneumoniae
was required for production of the soluble factor(s), HUVEC were infected with heat-inactivated
C. pneumoniae
or with viable organisms in the presence of chloramphenicol. Both treatments produced stimulation indices similar to those for live
C. pneumoniae
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 transduction events following chlamydia endocytosis may be important in the production of a soluble factor(s). The ability of
C. pneumoniae
to elicit an endothelial cell-derived soluble factor(s) that stimulates SMC proliferation may be important in the pathogenesis of atherosclerosis.
