gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Matrix metalloproteinase-2 (MMP-2) und -9 (MMP-9) cause glomerular inflammation in Goldblatt hypertensive rats

Matrix metalloproteinase 2 (MMP-2) und -9 (MMP-9) verursachen einen entzündlichen glomerulären Phänotyp in Ratten mit Goldblatt Hypertonie

Meeting Abstract (Hypertonie 2004)

  • U. Wenzel - UKE (Hamburg, D)
  • G. Wolf - UKE (Hamburg, D)
  • O. Steinmetz - UKE (Hamburg, D)
  • G. Zahner - UKE (Hamburg, D)
  • R. Stahl - UKE (Hamburg, D)
  • S. Harendza - UKE (Hamburg, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP54

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch054.shtml

Veröffentlicht: 10. August 2005

© 2005 Wenzel et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Introduction: Overexpression of MMP-2 causes inflammation of mesangial cells with activation, proliferation and matrix production (JBC 271:15074, 1995). An inflammatory phenotype is also found in 2 kidney, 1 clip hypertensive rats. It was therefore the aim to characterize the role of MMP-2 in hypertensive injury.

Methods: 6 weeks after clipping of the renal artery the clip was removed or treatment with enalapril (ENP) and hydrochlorothiazide was started. 4 weeks later glomerular inflammation was examined by FACS analysis of glomerular single cell suspension (ED-1), by western blotting (PCNA, Cyclin D1, alpha-smooth muscle cell actin (SMA), MMP-2), by gelatin zymography and by Realtime RT PCR (MMP-9, plasminogen activator inhibitor-1 (PAI-1)).

Results: Increased glomerular expression of MMP-2 (9.2fold) and MMP-9 (3.2fold) was found in hypertensive rats. Inflammation could be demonstrated by proliferation (PCNA and Cyclin D1 expression (13.3 and 3.1fold), activation (SMA 9fold) and collagen type IV deposition. FACS analysis showed glomerular infiltration by monocytes (25.8 vs. 8.6% in controls). Removal of the clip or ENP lowered blood pressure and decreased expression of MMP-2 and MMP-9. Expression of PCNA, Cyclin D1, SMA, monocyte infiltration and collagen IV staining were also normalized. The profibrotic molecule PAI-1 was upregulated in the nonclipped kidney (10.4fold) and normalized by both interventions.

Summary and conclusion: Increased glomerular expression of MMP-2 and MMP-9 is found in Goldblatt hypertensive rats. Lowering of blood pressure normalizes MMP-2 and MMP-9 expression as well as glomerular inflammation. Antihypertensive therapy causes regression of hypertensive injury in Goldblatt hypertensive rats by inhibition of PAI-1. In contrast, MMP-2 and MMP-9 do not contribute to the matrix degradation of hypertensive glomerular injury but are associated with an inflammatory phenotype and are a new target for treating hypertensive renal injury.