Complement activation in angiotensin II-induced organ damage

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Item Type:	Article
Title:	Complement activation in angiotensin II-induced organ damage
Creators Name:	Shagdarsuren, E., Wellner, M., Braesen, J.H., Park, J.K., Fiebeler, A., Henke, N., Dechend, R., Gratze, P., Luft, F.C. and Mueller, D.N.
Abstract:	We tested whether or not complement activation participates in angiotensin (Ang) II-induced vasculopathy. We used double transgenic rats harboring human renin and angiotensinogen genes (dTGR) with or without losartan or the human renin inhibitor aliskiren. Sprague-Dawley (SD) rats were controls. DTGR had increased blood pressure at week 5 that increased further by week 7. Albuminuria was absent at week 5 but increased markedly in weeks 6 and 7. C-reactive protein (CRP) elevation, macrophages, T cells, tumor necrosis factor (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 colocalized with interleukin (IL)-6. Losartan and aliskiren reduced albuminuria and complement expression. We also studied vascular smooth muscle cells (VSMC) from dTGR compared VSMC from SD. C3 and IL-6 mRNA were analyzed after Ang II, TNF-α, and CRP stimulation. VSMC from dTGR showed increased proliferation and C3 expression compared with SD. Ang II did not induce C3 mRNA in either VSMC type. However, TNF-α and CRP induced C3 mRNA slightly in SD VSMC but markedly in dTGR VSMC, whereas IL-6 induction was similar in both. Thus, complement activation and cell infiltration occurred before the onset of albuminuria in Ang II-mediated renal damage. TNF-α and CRP played a major role in C3 activation. VSMC from dTGR are more sensitive for C3 activation. Our data show that, in this Ang II-induced model, complement activation is a major participant and suggest that TNF-α and CRP may play a role in its induction.
Keywords:	Albuminuria and renal damage, Angiotensin II, Complement, Immune system, Animals, Rats
Source:	Circulation Research
ISSN:	0009-7330
Publisher:	American Heart Association
Volume:	97
Number:	7
Page Range:	716-724
Date:	18 August 2005
Official Publication:	https://doi.org/10.1161/01.RES.0000182677.89816.38
PubMed:	View item in PubMed

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