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

Lin, Zhihong; Fukuda, Noboru; Jin, Xue-Qing; Yao, En-Hui; Ueno, Takayoshi; Endo, Morito; Saito, Satoshi; Matsumoto, Koichí; Mugishima, Hideo

doi:10.1161/01.hyp.0000129540.83284.ca

Cited by 56 publications

(54 citation statements)

References 29 publications

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“…Recently, we demonstrated by microarray analysis that C3 mRNA is produced in smooth muscle from SHR in vivo but is not expressed in smooth muscle from Wistar Kyoto rats. In contrast, there were no differences in levels of mRNAs for C4, C8, and C9 in aortic smooth muscle cells from SHR and Wistar Kyoto rats (Lin et al, 2004). These data suggest that expression of C3 in VSMCs is independent of that of other complement system components and that C3 has unique effects on VSMCs.…”

Section: Discussionmentioning

confidence: 65%

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Complement 3 is involved in changing the phenotype of human glomerular mesangial cells

Wan

Fukuda

Endo

et al. 2007

Journal Cellular Physiology

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Complement activation contributes to tissue injury in various forms of glomerulopathy and is characterized by deposition of complement components, which accelerates the progression of chronic renal damage. We recently reported that complement 3 (C3), a critical component of the complement system, is associated with the synthetic phenotype of vascular smooth muscle cells. It is possible that C3 stimulates mesangial cells to assume the synthetic phenotype to, in turn, induce glomerular injury and sclerosis. We investigated the role of C3 in the growth and phenotype of mesangial cells. Cultured human mesangial cells (HMCs) expressed C3 mRNA and protein, and levels were increased in response to IFN-g and TNF-a. HMCs also expressed C3a receptor mRNA and protein. Exogenous C3a stimulated DNA synthesis in HMCs in a dose-dependent manner. C3a decreased expression h-caldesmon mRNA, a marker of the contractile phenotype, and increased the expression of osteopontin, matrix Gla, and collagen type1 a1 (collagen IV) mRNAs, which are markers of the synthetic phenotype. C3a decreased expression of a-smooth muscle actin in HMCs. Small interfering RNA (siRNA) targeting C3 reduced the DNA synthesis and proliferation of HMCs, increased expression of h-caldesmon mRNA, and decreased expression of osteopontin, matrix Gla, and collagen IV mRNAs in HMCs. These results indicate that C3 causes HMCs to convert to the synthetic phenotype and stimulates growth of mesangial cells, suggesting that C3 may play an important role in phenotypic regulation of mesangial cells in renal diseases.

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Section: Discussionmentioning

confidence: 65%

“…We found that complement 3 (C3) is expressed in spontaneously hypertensive rat (SHR)-derived VSMCs that show the synthetic phenotype and exaggerated growth. We found that C3 causes VSMCs to convert from the contractile to the synthetic phenotype to stimulate growth (Lin et al, 2004).…”

mentioning

confidence: 78%

Complement 3 is involved in changing the phenotype of human glomerular mesangial cells

Wan

Fukuda

Endo

et al. 2007

Journal Cellular Physiology

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“…A study of spontaneously hypertensive rats showed that C3 stimulated the exaggerated growth of vascular smooth muscle cells, independently of other complement factors. 23 Acylation stimulating protein (ASP) is produced by cleavage of C3. 31 ASP is a metabolically active molecule and has been associated with increased glucose uptake and fatty acid storage in the adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

“…22 A recent study of spontaneously hypertensive rats reported that C3 was produced by arterial smooth muscle cells, and importantly, that C3 stimulated the exaggerated growth of these cells. 23 However, to the best of our knowledge, no study has explored whether C3 or C4 predict the development of hypertension.…”

Section: Introductionmentioning

confidence: 99%

Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study

et al. 2006

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Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This populationbased longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hypertension. Incidence of hypertension and blood pressure increase over 15.7 (72.2) years follow-up was studied in relation to C3 and C4 at baseline. Among men with initially normal blood pressure (o160/95 mm Hg), incidence of hypertension (X160/95 mm Hg or treatment) was 32, 42, 37 and 47%, respectively, for men with C3 in the first, second, third and fourth quartile (trend: P ¼ 0.001). This relationship remained significant after adjustment for confounding factors. Among men without blood pressure treatment, systolic BP increase (mean þ standard error, adjusted for age, initial blood pressure and follow-up time) was 17.5 þ 0.8, 19.6 þ 0.9, 19.8 þ 0.8 and 20.8 þ 0.8 mm Hg, respectively, in the C3 quartiles (trend: P ¼ 0.004). C3 was not associated diastolic blood pressure at followup. Although C4 was associated with blood pressure at the baseline examination, there was no relationship between C4 and development of hypertension or future blood pressure increase. It is concluded that C3 in plasma is associated with future blood pressure increase and development of hypertension.

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“…The article by Lin et al in this issue 3 describes an important finding of a differential expression of the complement protein C3 in the exaggerated growth of arterial smooth muscle cells from SHRs of an age (3 weeks) that precedes measurable increases in blood pressure. The authors first study medial tissues from whole arteries and, using gene chip analyses, demonstrate that several genes are expressed in SHR tissues but not Wistar-Kyoto rat (WKY) tissues; other genes are expressed in both but at either lower or higher levels in SHRs versus WKYs.…”

Section: Complementmentioning

confidence: 99%

C3 or Not C3

Watts

2004

Hypertension

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

Cited by 56 publications

References 29 publications

Complement 3 is involved in changing the phenotype of human glomerular mesangial cells

Complement 3 is involved in changing the phenotype of human glomerular mesangial cells

Plasma levels of complement C3 is associated with development of hypertension: a longitudinal cohort study

C3 or Not C3

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