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Reversal of angiogenic growth factor upregulation by revascularization of lower limb ischemia

Porcu, Paolo and Emanueli, Costanza and Kapatsoris, Maria and Chao, Julie and Chao, Lee and Madeddu, Paolo Roberto (2002) Reversal of angiogenic growth factor upregulation by revascularization of lower limb ischemia. Circulation, Vol. 105 (1), p. 67-72. eISSN 1524-4539. Article.

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DOI: 10.1161/hc0102.101360


Background— Tissue kallikrein (tK) and vascular endothelial growth factor (VEGF) are potent angiogenic agents. Upregulation of tK or VEGF was documented in animal models of acute ischemia, yet it remains unknown whether these endothelial cell mitogens are overexpressed in chronic peripheral vascular insufficiency.
Methods and Results— Circulating tK and VEGF were measured in 36 patients with symptomatic peripheral vascular disease before and after surgical revascularization. In 6 patients without symptoms at rest, tK was assayed after exercise stress test. VEGF levels fell within the normal range in all patients (96±11 versus 109±13 pg/mL in healthy control subjects, P=NS) and remained unchanged after revascularization. In contrast, tK expression was upregulated in 34 of 36 patients (1107±203 versus 85±10 pg/mL in control subjects, P<0.05), with no further increase after exercise. Tissue kallikrein levels in the venous effluent of ischemic limbs were found to be positively correlated with the number of angiographically recognizable collateral vessels (P<0.001). Follow-up studies documented reversal of tK upregulation after revascularization (P<0.01), whereas no change was observed in venous samples from untouched legs.
Conclusions— Induction of tK could represent a compensatory response to chronic arterial insufficiency, attempting to maintain an adequate tissue perfusion. Heterogeneous statement of growth factors may have important implications in reparative and therapeutic angiogenesis.

Item Type:Article
ID Code:679
Uncontrolled Keywords:Angiogenesis, atherosclerosis, bradykinin, revascularization
Subjects:Area 06 - Scienze mediche > MED/22 Chirurgia vascolare
Area 06 - Scienze mediche > MED/18 Chirurgia generale
Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
002 Altri enti e centri di ricerca del Nord Sardegna > National laboratory of the national institute of biostructures and biosystems, Osilo > Cardiovascular medicine and gene therapy Section
001 Università di Sassari > 03 Istituti > Clinica chirurgica generale e terapia chirurgica
Publisher:Lippincott Williams & Wilkins
Copyright Holders:© 2002 American Heart Association
Deposited On:18 Aug 2009 10:02

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