Published Online
on May 10, 2004

A more recent version of this article appeared on July 1, 2004

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Submitted on January 26, 2004
Revised on February 24, 2004

Complement 3 Is Involved in the Synthetic Phenotype and Exaggerated Growth of Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats

Zhi-Hong Lin; Noboru Fukuda^*; Xue-Qing Jin; En-Hui Yao; Takahiro Ueno; Morito Endo; Satoshi Saito; Koichi Matsumoto; and Hideo Mugishima

From the Second Department of Internal Medicine (Z.-H.L., N.F., X.-Q.J., E.-H.Y., T.U., M.E., S.S., K.M.) and Department of Advanced Medicine (H.M.), Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, Tokyo, Japan.

^* To whom correspondence should be addressed. E-mail: fukudan{at}med.nihon-u.ac.jp.

Abstract--Vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) show the synthetic phenotype and exaggerated growth in comparison with VSMCs from normotensive Wistar-Kyoto (WKY) rats. We investigated genes associated with the synthetic phenotype and exaggerated growth of VSMCs from SHR by microarray. Expression of 1300 transcripts was evaluated by microarray with total mRNA extracted from mid-layer aortic smooth muscle of 3-week-old SHR/Izumo and WKY/Izumo rats. mRNAs encoding sodium-dependent neurotransmitter transporter, epidermal growth factor precursor, EEF2, leptin receptor long-isoform b, clathrin assembly protein short form, and preprocomplement 3 (pre-pro-C3) were expressed only in aortic smooth muscle from SHR by microarray and by reverse-transcription polymerase chain reaction analysis. Pre-pro-C3 mRNA was detected only in cultured VSMCs from SHR. Exogenous C3 changed VSMCs to the synthetic phenotype. Antisense oligodeoxynucleotides (ODN) to C3 reduced the higher level of DNA synthesis in VSMCs from SHR. Antisense ODN to C3 increased expression of SM22 mRNA and decreased expression of osteopontin and matrix Gla mRNAs. It also decreased expression of growth factor mRNAs in VSMCs from SHR. In conclusion, we have shown that C3, independent of other complement molecules, has direct effects on the phenotype of VSMCs and stimulates growth of these cells. C3 is produced only by VSMCs from SHR. Therefore, C3 may be the gene underlying the synthetic phenotype and exaggerated growth of VSMCs from SHR. C3 may be a new target for the treatment of hypertension.

Key words: hypertrophy • remodeling • rats • muscle, smooth, vascular

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