Hyperthermia at 43°C for 2 h Inhibits the Proliferation of Vascular Smooth Muscle Cells, but not Endothelial Cells

K. Orihara, S. Biro, S. Hamasaki, H. Eto, M. Miyata, Y. Ikeda and C. Tei. Hyperthermia at 43°C for 2 h Inhibits the Proliferation of Vascular Smooth Muscle Cells, but not Endothelial Cells. Journal of Molecular and Cellular Cardiology (2002) 34, 1205–1215. Restenosis after angioplasty is one of the most critical problems of the various interventional therapies for myocardial ischemia. It has been difficult to prevent the vascular smooth muscle cells (VSMCs) proliferation resulting in restenosis. The goal of this study was to prove the treatment by hyperthermia to be effective in suppressing VSMCʹs proliferation in vitro. When just-stimulated VSMCs, which were incubated for 2 h after 5% FBS stimulation to quiescent VSMCs, were exposed to hyperthermia (43°C, 2 h), the cell cycle progression to S and G2/M phase was significantly delayed 24 h after 5% FBS stimulation. And another 24 h later, cell death was observed partly (19%) of heat-treated VSMCs. Nonetheless, hyperthermia under the same conditions did not result in the death of quiescent VSMCs, and did not inhibit the proliferation of cultured bovine aortic endothelial cells (BAECs). In addition, we found that hyperthermia (43°C, 2 h) elevated p27Kip1 over the amount induced in confluent VSMCs. Much elevation of p27Kip1, which is a negative regulator of G1/S progression, may play a role in heat-induced G1 arrest of VSMCs. In conclusion, we have found that hyperthermia (43°C, 2 h) inhibited the proliferation of the dividing VSMCs mainly due to G1 arrest with neither inhibiting the generation of BAECs nor damaging quiescent VSMCs. Hence, our data suggest that hyperthermia may be clinically applicable for the prevention of restenosis.