Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia

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

doi:10.1161/01.CIR.103.1.125

Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia

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

Research output: Contribution to journal › Article › peer-review

Abstract

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 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.

Original language	English (US)
Pages (from-to)	125-132
Number of pages	8
Journal	Circulation
Volume	103
Issue number	1
DOIs	https://doi.org/10.1161/01.CIR.103.1.125
State	Published - Jan 9 2001
Externally published	Yes

Keywords

Angiogenesis
Bradykinin
Gene therapy
Ischemia
Muscles

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1161/01.CIR.103.1.125

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Emanueli, C., Minasi, A., Zacheo, A., Chao, J., Chao, L., Salis, M. B., Straino, S., Tozzi, M. G., Smith, R., Gaspa, L., Bianchini, G., Stillo, F., Capogrossi, M. C., & Madeddu, P. (2001). Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia. Circulation, 103(1), 125-132. https://doi.org/10.1161/01.CIR.103.1.125

Emanueli, C, Minasi, A, Zacheo, A, Chao, J, Chao, L, Salis, MB, Straino, S, Tozzi, MG, Smith, R, Gaspa, L, Bianchini, G, Stillo, F, Capogrossi, MC & Madeddu, P 2001, 'Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia', Circulation, vol. 103, no. 1, pp. 125-132. https://doi.org/10.1161/01.CIR.103.1.125

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abstract = "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 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.",

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AU - Emanueli, Costanza

AU - Minasi, Alessandra

AU - Zacheo, Antonella

AU - Chao, Julie

AU - Chao, Lee

AU - Salis, Maria Bonaria

AU - Straino, Stefania

AU - Tozzi, Maria Grazia

AU - Smith, Robert

AU - Gaspa, Leonardo

AU - Bianchini, Giuseppe

AU - Stillo, Francesco

AU - Capogrossi, Maurizio C.

AU - Madeddu, Paolo

PY - 2001/1/9

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N2 - 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 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.

AB - 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 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.

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Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia

Abstract

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