gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

Article

Send article

Characterisation of the cardiac kallikrein-kinin system in transgenic rats expressing the human KLK-1 gene

Charakterisierung des kardialen Kallikrein-Kinin-Systems bei transgenen Ratten mit Expression des humanen hKLK-1 Gens

Meeting Abstract (Hypertonie 2004)

Search Medline for

  • M. Koch - Charité - Universitätsmedizin in Berlin (Berlin, D)
  • F. Spillmann - Charité - Universitätsmedizin in Berlin (Berlin, D)
  • M. Dorenkamp - Charité - Universitätsmedizin in Berlin (Berlin, D)
  • C. Altmann - Charité - Universitätsmedizin in Berlin (Berlin, D)
  • A. Dendorfer - Institut für exp. u. klin. Pharma- u. Toxikologie (Lübeck, D)
  • F. Escher - Institut für exp. u. klin. Pharma- u. Toxikologie (Lübeck, D)
  • M. Noutsias - Max Delbrück Zentrum für Molekulare Medizin (Berlin, D)
  • M. Bader - Max Delbrück Zentrum für Molekulare Medizin (Berlin, D)
  • T. Walther - Charité Unversitätsmedizin in Berlin (Berlin, D)
  • H.-P. Schultheiss - Charité Unversitätsmedizin in Berlin (Berlin, D)
  • C. Tschöpe - Charité Unversitätsmedizin in Berlin (Berlin, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP51

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2004/04hoch051.shtml

Published: August 10, 2005

© 2005 Koch et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective: The kallikrein-kinin system (KKS) is an established myocardial protection system under ischemic conditions. We analyzed the bradykinin (BK) content in the coronary outflow ex vivo and the BK receptor regulation and capillary density in vivo in transgenic rats harbouring the human tissue kallikreine-1 gene TGR(hKLK1) compared to wild-type Spraque Dawley rats under basal conditions

Methods: Coronary outflow of buffer-perfused isolated hearts of controls and TGR(hKLK1) was immediately supplemented with 1% triflouroacetic acid. And BK content was quantitated by a specific radioimmunoassay. The expression of BK B1 und B2 receptor mRNA was detected by a ribonuclease protection assay with GAPDH mRNA as a housekeeping gene. CD31 expression as a marker for cardiac capillary density was analyzed by immunohistochemical staining and quantified by digital image analysis.

Results: Basal BK content was 3.5-fold increased in TGR(hKLK1) (0.98±0.20 pg/ml vs. 0.28±0.08 pg/ml; p<0.01) compared to controls. Also expression of BK receptor mRNA was significantly increased in TGR(hKLK1) (B1-Rezeptor: 316±42 vs. 100±41%; B2: 394±9 vs. 100±16%). This was accompanied by a significant higher CD31 expression in TGR(hKLK1) (Area fraction: 0.03 (0.02 -0.05) vs. 0.06 (0.04 - 0.08); p<0.05).

Conclusion: We detected both an increased basal BK content as well as an higher BK receptor expression in our TGR(hKLK1) model, indicating an activated KKS. The KKS upregulation was accompanied by a pro-angiogenetic effect with higher capillary density.