Functional Blockade of Platelet-Derived Growth Factor Receptor-β but Not of Receptor-α Prevents Vascular Smooth Muscle Cell Accumulation in Fibrous Cap Lesions in Apolipoprotein E–Deficient Mice

• DOI: 10.1161/01.cir.103.24.2955
• Publication Date: 2012-06-12T00:09:32Z
• Authors: Hideto Sano; Tetsuo Sudo; Masayuki Yokode; Toshinori Murayama; Hiroshi Kataoka; Nobuyuki Takakura; Satomi Nishikawa; Shin-Ichi Nishikawa; Toru Kita
• Keywords: Platelet-derived growth factor; Fibrous cap

Background —The vascular smooth muscle cell (VSMC) is the central component involved in fibroproliferative response atherogenesis. As lesion advances, VSMCs migrate from media into subendothelial space, thereby forming fibrous plaque lesions. Platelet-derived growth factor (PDGF) has been known to be a potent chemoattractant and mitogen for SMCs, but pathophysiological role of 2 PDGF receptors, receptor-α (PDGFR-α) receptor-β (PDGFR-β) atherogenesis poorly understood. To clarify this problem, we prepared antagonistic rat monoclonal antibodies, APA5 APB5, against murine PDGFR-α PDGFR-β, respectively. Methods Results —Apolipoprotein E–deficient mice were fed high-fat diet containing 0.3% cholesterol 6 weeks age subjected injection with 1 mg/d IP either antibody 12 18 every other day. In injected aortic atherosclerotic size number intimal reduced by 67% 80%, respectively, compared control irrelevant IgG. contrast, that received showed only minimal reduction size, large observed intima. intima advanced lesions, APB5 immunolabeled VSMCs, whereas could detect mainly media. Conclusions —These results indicate PDGFR-β plays significant formation lesions regulation signal transduction through affect mice.