P194	C-reactive protein and complement in angiotensin II-induced organ damage.
1E.Shagdarsuren, 1M.Wellner, 1J-H.Braesen, 2J-K.Park, 1N.Henke, 1R.Dechend, 1P.Gratze, 1A.Fiebeler, 1F.C.Luft, 1D.N.Mueller
1HELIOS Klinik, Charite, Campus-Buch, Berlin, DE; 2Department of Medicine-Nephrology, Hannover Medical School, Hannover, DE.

The role of complement and C-reactive protein (CRP) in Ang II-induced vasculopathy is not defined. We studied complement in an Ang II model and tested whether complement activation in the kidneys precedes or is the consequence of albuminuria. We also analyzed whether complement C3 is induced differently in smooth muscle cells (VSMC) with a synthetic compared with the contractile phenotype. We used double transgenic rats harboring human renin and angiotensinogen genes (dTGR) with or without losartan (LOS). Sprague-Dawley (SD) rats were controls. C3 and IL-6 mRNA were analyzed in VSMC isolated from dTGR and SD after Ang II, TNF-α, and CRP stimulation. DTGR showed moderately increased blood pressure at week 5 that peaked at week 7. Albuminuria was absent at week 5, but increased markedly in weeks 6 and 7. CRP elevation, macrophages, T-cells, TNF-α, C1q, C3, C3c, and C5b-9 expression preceded albuminuria. C1q, C3, C3c, and C5b-9 were observed in the dTGR vessel media. C5b-9 co-localized with IL-6. LOS reduced albuminuria and complement expression. VSMC from dTGR showed increased proliferation and C3 expression, compared to SD. Ang II did not induce C3 mRNA in either VSMC phenotype. TNF-α and CRP induced C3 mRNA slightly in contractile, but massively in synthetic VSMC. IL-6 induction was similar in both VSMC phenotypes. Thus, complement activation and cell infiltration occur before the onset of albuminuria in Ang II-mediated renal damage. Synthetic VSMC are more sensitive for C3 activation. TNF-? and CRP play a major role in C3 activation observed in our rat model.

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