Document Detail

Reversal of angiogenic growth factor upregulation by revascularization of lower limb ischemia.
MedLine Citation:
PMID:  11772878     Owner:  NLM     Status:  MEDLINE    
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.
Paolo Porcu; Costanza Emanueli; Maria Kapatsoris; Julie Chao; Lee Chao; Paolo Madeddu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2002-01-04     Completed Date:  2002-04-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  67-72     Citation Subset:  AIM; IM    
Institute of Internal Medicine, Medical University of Sassari, Sassari, Italy.
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MeSH Terms
Endothelial Growth Factors / blood*
Follow-Up Studies
Ischemia / blood,  therapy*
Leg / blood supply*
Lymphokines / blood*
Middle Aged
Peripheral Vascular Diseases / blood,  therapy
Tissue Kallikreins / blood*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Lymphokines; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; EC Kallikreins

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