Artikel
Complement Activation in Angiotensin II-Induced Organ Damage
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Veröffentlicht: | 8. August 2006 |
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Gliederung
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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 (LOS) or the human renin inhibitor aliskiren (ALISK). 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. CRP elevation, macrophages, T-cells, TNF-a, 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 and ALISK 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-a, and C-reactive protein (CRP) stimulation. VSMC from dTGR showed increased proliferation and C3 expression, compared to SD. Ang II did not induce C3 mRNA in either VSMC type. However, TNF-a and CRP induced C3 mRNA slightly in SD VSMC, but markedly in dTGR VSMC, while 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-a 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-a and CRP may play a role in its induction.