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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
Open accessAbstract
Background —The vascular smooth muscle cell (VSMC) is the central cell component involved in the fibroproliferative response in atherogenesis. As the lesion advances, VSMCs migrate from the media into the 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 the pathophysiological role of the 2 PDGF receptors, receptor-α (PDGFR-α) and receptor-β (PDGFR-β) in atherogenesis is poorly understood. To clarify this problem, we prepared antagonistic rat monoclonal antibodies, APA5 and APB5, against murine PDGFR-α and PDGFR-β, respectively. Methods and Results —Apolipoprotein E–deficient mice were fed a high-fat diet containing 0.3% cholesterol from 6 weeks of age and subjected to injection with 1 mg/d IP of either antibody from 12 to 18 weeks every other day. In the mice injected with APB5, the aortic atherosclerotic lesion size and the number of intimal VSMCs were reduced by 67% and 80%, respectively, compared with the control mice injected with irrelevant rat IgG. In contrast, the mice that received APA5 showed only minimal reduction of lesion size, and a large number of VSMCs were observed in the intima. In the intima of advanced lesions, APB5 immunolabeled VSMCs, whereas APA5 could detect VSMCs mainly in the media. Conclusions —These results indicate that PDGFR-β plays a significant role in formation of fibrous atherosclerotic lesions and that regulation of the signal transduction through PDGFR-β could affect atherogenesis in mice.
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“In mice, the fibrous cap VSMCs are derived from medial VSMCs 22,138 that have undergone migration and proliferation in response to cytokines and growth factors, such as PDGF, derived from macrophages and activated ECs 23,129,139 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [139]
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Metadata
- Authors
- Sano, H., Sudo, T., Yokode, M., Murayama, T., Kataoka, H., Takakura, N., Nishikawa, S., Nishikawa, S.-I., & Kita, T.
- Affiliations
- Kyoto University (JP)
- Venue
- Circulation
- Published
- 2001-06-19
- Volume
- 103
- Issue
- 24
- Pages
- 2955-2960
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1963798186
- Cited by
- 169
- References
- 31
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 9 · 2017: 6 · 2016: 6 · 2015: 10 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- platelet-derived growth factor, PDGF receptor beta, PDGF receptor alpha, vascular smooth muscle cells, atherosclerosis, fibrous cap, intimal thickening, monoclonal antibodies, ApoE-deficient mice, high-fat diet, VSMC migration, atherogenesis
- MeSH terms
- Animals, Antibodies, Monoclonal, Aorta, Apolipoproteins E, Arteriosclerosis, Bone Marrow Cells, Cell Count, Cells, Cultured, Colony-Forming Units Assay, Diet, Atherogenic, Disease Models, Animal, Fibrosis, Immunohistochemistry, Injections, Intraperitoneal, Muscle, Smooth, Vascular, Sinus of Valsalva, Signal Transduction, Rats, Wistar, Mice, Knockout, Disease Progression, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Mice, Rats
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