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EnglishBackground—Human tissue kallikrein (HK) releases kinins from kininogen. We investigated whether adenovirus-mediated HK gene delivery is angiogenic in the context of ischemia. Methods and Results—Hindlimb ischemia, caused by femoral artery excision, increased muscular capillary density (P<0.001) and induced the expression of kinin B1 receptor gene (P<0.05). Pharmacological blockade of B1 receptors blunted ischemia-induced angiogenesis (P<0.01), whereas kinin B2 receptor antagonism was ineffective. Intramuscular delivery of adenovirus containing the HK gene (Ad.CMV-cHK) enhanced the increase in capillary density caused by ischemia (969±32 versus 541±18 capillaries/mm2 for control, P<0.001), accelerated blood flow recovery (P<0.01), and preserved energetic charge of ischemic muscle (P<0.01). Chronic blockade of kinin B1 or B2 receptors prevented HK-induced angiogenesis. Conclusions—HK gene delivery enhances the native angiogenic response to ischemia. Angiogenesis gene therapy with HK might be applicable to peripheral occlusive vascular disease.
| Autori interni: | |
| Autori: | Emanueli, C.; Minasi, A.; Zacheo, A.; Chao, J.; Chao, L.; Salis, Mb; Straino, S.; Tozzi, MARIA GRAZIA; Gaspa, L.; Stillo, F.; Capogrossi, Mc; Madeddu, P. |
| Titolo: | Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia |
| Anno del prodotto: | 2001 |
| Digital Object Identifier (DOI): | 10.1161/01.CIR.103.1.125 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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