Abstract

Atherosclerosis is a vascular disorder involving inflammation, a narrowed vascular lumen in the entire tunica intima, and reduced elasticity of the arterial wall. It has been found that Hsp60 from Chlamydia pneumoniae, an obligate bacterial pathogen associated with atheroma lesions, mimics human Hsp60, thereby causing attacks by immune cells on stressed endothelial cells expressing endogenous Hsp60 on their surface. Furthermore, Hsp60 from C. pneumoniae has been shown to promote the growth of vascular smooth muscle cells (VSMCs). To explore probes that can be used for studying signal transduction elicited by the chlamydial Hsp60, we have tested several natural products for their inhibitory actions on the Hsp60-induced proliferation of rat arterial smooth muscle cells. Sesamol, vanillyl alcohol, and trans-ferulic acid exhibited moderate inhibitory actions on the Hsp60-induced cell proliferation; zerumbone, humulene, and caryophylene effectively inhibited it at low concentrations with IC(50) values of 529, 122, and 110 nM, respectively. The results indicated that the 11-membered alicyclic ring is favorable for interactions with receptors involved in the Hsp60-induced VSMC proliferation.

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