The role of heat shock protein-60 in vascular smooth muscle cell proliferation and atherosclerotic development

Abstract

This study investigated whether heat shock protein-60 (Hsp60) modulates nuclear protein import (NPI) to promote vascular smooth muscle cell (VSMC) proliferation and atherosclerotic development. Rat VSMCs were treated with oxidized low density lipoprotein (oxLDL), which increased Hsp60 expression, NPI machinery expression, and cell proliferation versus controls. Overexpression of cytosolic Hsp60 induced VSMC proliferation and enhanced NPI. Conversely, Hsp60 knockdown followed by oxLDL treatment did not increase NPI, NPI machinery or proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Co-immunoprecipitation showed that at high intracellular levels, Hsp60 interacts with Ran, a protein involved in NPI. Plaques obtained from hypercholesterolemic rabbit aortas showed that Hsp60, PCNA and Nup62 expression were elevated during plaque growth and returned to baseline during plaque stabilization. Thus, intracellular Hsp60 enhances NPI and VSMC proliferation through a chaperone and signaling mechanism, processes that may contribute to atherosclerotic development.