1. Role of complement 3a in the synthetic phenotype and angiotensin II-production in vascular smooth muscle cells from spontaneously hypertensive rats.
- Author
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Han Y, Fukuda N, Ueno T, Endo M, Ikeda K, Xueli Z, Matsumoto T, Soma M, and Matsumoto K
- Subjects
- Angiotensin II drug effects, Animals, Arginine pharmacology, Cells, Cultured, Hypertension metabolism, Kruppel-Like Transcription Factors drug effects, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular metabolism, Phenotype, RNA, Messenger drug effects, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Receptors, Complement drug effects, Angiotensin II biosynthesis, Arginine analogs & derivatives, Benzhydryl Compounds pharmacology, Complement C3a physiology, Hypertension immunology, Muscle, Smooth, Vascular immunology, Receptors, Complement antagonists & inhibitors
- Abstract
Background: Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMCs) show exaggerated growth with a synthetic phenotype and angiotensin II (Ang II)-production. To evaluate the contribution of complement 3 (C3) or C3a toward these abnormalities in SHR, we examined effects of a C3a receptor inhibitor on proliferation, phenotype, and Ang II-production in VSMCs from SHR and Wistar-Kyoto (WKY) rats., Methods: Expression of pre-pro-C3 messenger RNA (mRNA) and C3 protein was evaluated by reverse transcription-PCR and western blot analyses, and C3a receptor mRNA was evaluated by reverse transcription-PCR analysis in quiescent VSMCs from SHR and WKY rats. We examined the effects of the C3a inhibitor, SB290157, on proliferation and the expression of phenotype-marker and Krueppel-like factor 5 (KLF-5) mRNAs in VSMCs from SHR and WKY rats. We examined effects of C3a receptor inhibitor, SB290157, on Ang II-production in conditioned medium of VSMCs from SHR and WKY rats by a radioimmunoassay., Results: Expression of pre-pro-C3 mRNA and C3 protein was significantly higher in SHR VSMCs than WKY VSMCs. SB290157 significantly inhibited proliferation of VSMCs from SHR, but not in cells from WKY rats. Relative to WKY VSMCs, SB290157 significantly increased the low expression of SM22α mRNA and decreased the high expression of osteopontin mRNA in SHR VSMCs. SB290157 significantly decreased the high expression of KLF-5 and Ang II-production in VSMCs from SHR, but not in cells from WKY rats., Conclusions: C3a induces exaggerated growth, a synthetic phenotype and Ang II-production in SHR-derived VSMCs. C3a may be primarily involved in cardiovascular remodeling in hypertension., (© 2012 American Journal of Hypertension, Ltd.)
- Published
- 2012
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