Portal de Periódicos da CAPES

Local Delivery of Human Tissue Kallikrein Gene Accelerates Spontaneous Angiogenesis in Mouse Model of Hindlimb Ischemia

2001; Lippincott Williams & Wilkins; Volume: 103; Issue: 1 Linguagem: Inglês

10.1161/01.cir.103.1.125

1524-4539

Costanza Emanueli, Alessandra Minasi, Antonella Zacheo, Julie Chao, Lee Chao, Maria Bonaria Salis, Stefania Straino, Maria Grazia Tozzi, Robert S. Smith, Leonardo Gaspa, Giuseppe Bianchini, Francesco Stillo, Maurizio C. Capogrossi, Paolo Madeddu,

Neurobiology and Insect Physiology Research

Background —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 B 1 receptor gene ( P <0.05). Pharmacological blockade of B 1 receptors blunted ischemia-induced angiogenesis ( P <0.01), whereas kinin B 2 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/mm 2 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 B 1 or B 2 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.