Hyperthermia at 43 degrees C for 2h inhibits the proliferation of vascular smooth muscle cells, but not endothelial cells.
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 VSMC's proliferation in vitro. When just-stimulated VSMCs, which were incubated for 2h after 5% FBS stimulation to quiescent VSMCs, were exposed to hyperthermia (43 degrees C, 2h), the cell cycle progression to S and G2/M phase was significantly delayed 24h after 5% FBS stimulation. And another 24h 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 degrees C, 2h) elevated p27(Kip1) over the amount induced in confluent VSMCs. Much elevation of p27(Kip1), 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 degrees C, 2h) 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.
Orihara
Koji
K
The First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
Biro
Sadatoshi
S
Hamasaki
Shuichi
S
Eto
Hideyuki
H
Miyata
Masaaki
M
Ikeda
Yoshiyuki
Y
Tei
Chuwa
C
D000818:Animals; D001013:Aorta, Thoracic; D002417:Cattle; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D016923:Cell Death; D002455:Cell Division; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004730:Endothelium, Vascular / Q000166:cytology; D006979:Hyperthermia, Induced; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27