Acute and chronic smooth muscle cell apoptosis after mechanical vascular injury can occur independently of the Fas-death pathway.
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.
Sata
M
M
Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Tokyo, Japan. sata-2im@h.u-tokyo.ac.jp
Sugiura
S
S
Yoshizumi
M
M
Ouchi
Y
Y
Hirata
Y
Y
Nagai
R
R
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000473:pathology*; D053222:Fas Ligand Protein; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D015398:Signal Transduction; D013314:Stress, Mechanical; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor