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The Role of Bradykinin Receptors in Arteriogenesis: from molecular concepts to therapeutic modulation
Author(s) -
Hillmeister Philipp,
Noble Ferdinand,
Gatzke Nora,
Dülsner André,
Bader Michael,
Schadock Ines,
Troidl Kerstin,
Jung Georg,
Bondke Anja,
Höfer Imo,
Buschmann Ivo
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1092.20
Subject(s) - arteriogenesis , agonist , bradykinin , receptor , bone marrow , perfusion , medicine , pharmacology , inflammation , endocrinology , chemistry , angiogenesis
Collateral artery growth is accompanied by kininogen expression, the substrate for kinins which signal via bradykinin receptors 1 and 2 (B1R, B2R). Here, the role of BR signaling in peripheral and cerebral arteriogenesis was analysed in the femoral artery occlusion (FAO) model in mice (C57Bl/6, B1R−/−, B2R −/−), and in rats (sprague dawley), which were subjected to 3‐vessel occlusion (3‐VO). Arteriogenesis was modulated therapeutically by the application of B1R and B2R agonists/antagonists and the mechanism of B1R signaling in arteriogenesis was elucidated by performing crosswise bone marrow transplantation (B1R −/−, WT). 7 days post FAO BR −/− mice show significant reduction of collateral perfusion, with B1R −/− mice exhibiting the strongest phenotype (−50%). Arteriogenesis can be inhibited by B1R and B2R antagonists and stimulated by B1R agonists. Injection of WT bone marrow into B1R −/− rescued the impaired arteriogenesis of B1R deficient mice and vice versa collateral perfusion was reduced to levels of B1R −/− mice. Histological immunostainings validated inhibition/induction of leucocyte migration in response to selective B1R antagonist/agonist treatment. In conclusion, BRs are relevant for collateral artery growth, which can be therapeutically modulated by BR antagonists/agonists, and in particular depend on B1R expression on bone‐marrow derived cells. Support: CSB, BMBF Germany