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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1733.)
© 2001 American Heart Association, Inc.

Vascular Biology

Acute and Chronic Smooth Muscle Cell Apoptosis After Mechanical Vascular Injury Can Occur Independently of the Fas-Death Pathway

Masataka Sata; Seiryo Sugiura; Masao Yoshizumi; Yasuyoshi Ouchi; Yasunobu Hirata; Ryozo Nagai

From the Department of Cardiovascular Medicine (M.S., S.S., Y.H., R.N.) and the Department of Geriatric Medicine (M.Y., Y.O.), University of Tokyo, Graduate School of Medicine, Tokyo, Japan.

Correspondence to Dr Masataka Sata, Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail sata-2im{at}h.u-tokyo.ac.jp

Abstract—— Vascular smooth muscle cell (VSMC) apoptosis has been demonstrated in vascular lesions, such as atherosclerotic and postangioplasty restenotic lesions. Balloon injury also induces VSMC apoptosis. Fas is a death factor that mediates apoptosis when it is activated by its ligand, FasL. Fas-mediated apoptosis was found to be implicated in the pathogenesis of vascular diseases in which Fas/FasL expression was detected. We investigated whether the Fas/FasL interaction mediated acute and chronic VSMC apoptosis and lesion formation in a vascular injury model that may resemble balloon angioplasty. A large spring wire was inserted into the femoral artery of C3H/HeJ (wild-type), C3H-gld (Fas ligand-/-), and C3H-lpr (Fas-/-) mice. The wire was left in place for 1 minute to denude and expand the artery. Massive apoptosis was observed in medial VSMCs from 1 to 7 hours later. There was no difference in the number of apoptotic cells among the 3 groups of mice 4 hours after injury. At 4 weeks, the injured arteries presented signs of concentric neointimal hyperplasia composed exclusively of VSMCs. There was no difference in the degree of neointima hyperplasia (intima/media ratios were as follows: wild type 1.4±0.3, gld 1.0±0.2, and lpr 1.3±0.2) or in the number of apoptotic nuclei among the 3 groups. These findings suggest the existence of other signaling pathways for acute and chronic VSMC apoptosis, at least that induced by mechanical vascular injury.

Key Words: Fas • apoptosis • balloon injury • smooth muscle cells • intima

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