Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: a link between angiogenesis and thrombogenesis?

2003 ◽  
Vol 104 (4) ◽  
pp. 397-404 ◽  
Author(s):  
Andrew J. MAKIN ◽  
Natalia A.Y. CHUNG ◽  
Stanley H. SILVERMAN ◽  
Gregory Y.H. LIP

Increasing evidence points towards a prothrombotic state in atherosclerosis and its manifestations, such as peripheral artery disease (PAD), which is associated with thrombosis-related complications, such as acute limb ischaemia, graft thrombosis and stroke. We hypothesized that the increased risk of thrombogenesis in PAD may be related to abnormal angiogenesis and, thus, an increased risk of future vascular disease. To test this hypothesis, we measured plasma levels of tissue factor (TF) and related levels to indices of angiogenesis, that is vascular endothelial growth factor (VEGF) and its soluble receptor sFlt-1. We studied 234 patients (145 males; mean age 68.6±10 years) with proven PAD (ankle brachial pressure index <0.8) and compared them with 50 healthy controls. Levels of VEGF (P = 0.001) and TF (P = 0.043) were increased in patients compared with controls. There were significant correlations between VEGF and TF levels in both patients (Spearman r = 0.351, P<0.001) and healthy controls (Spearman r = 0.335, P = 0.017). Amongst PAD patients, levels of VEGF were related to gender, with women having higher levels than men. There was no difference in the levels of sFlt-1 between the patients and controls, or between the subgroups of patients. There were however significant correlations between the levels of sFlt-1 and TF (Spearman r = 0.268, P<0.001) and between sFlt-1 and VEGF (Spearman r = 0.499, P<0.001). In conclusion, patients suffering from proven PAD have higher plasma levels of TF and VEGF compared with controls, with a significant correlation between the two. This suggests a link between the hypercoagulable state in PAD and the process of angiogenesis.

2002 ◽  
Vol 102 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Andrew D. BLANN ◽  
Funmi M. BELGORE ◽  
Charles N. McCOLLUM ◽  
Stanley SILVERMAN ◽  
Peck Lin LIP ◽  
...  

Since atherosclerosis is characterized by endothelial damage, re-growth seems likely to be occurring in order to repair or replace injured cells. Angiogenic vascular endothelial growth factor (VEGF), a likely mediator of these events, acts on the endothelium via a specific receptor, Flt-1. We hypothesized that patients with different manifestations of atherosclerosis, and others with diabetes, would have altered plasma levels of VEGF and Flt-1 compared with healthy individuals. Accordingly, 70 patients with peripheral artery disease (PAD), 70 patients with coronary artery disease (CAD), and 70 age- and sex-matched healthy controls were recruited. We also recruited 14 patients with diabetes asymptomatic for atherosclerosis, 14 patients with diabetes and atherosclerosis, and 14 age- and sex-matched controls. VEGF and soluble Flt-1 (sFlt-1) were measured by ELISA. In the main study of PAD and CAD, VEGF was raised in both patient groups (P < 0.05) compared with the controls, but was not different between the patient groups. sFlt-1 was lower in patients with PAD (P < 0.05), but not in those with CAD, compared with the controls. VEGF was raised in the patients with diabetes plus atherosclerosis (P < 0.05), but not in the group with diabetes alone; levels of sFlt-1 were unaltered in both diabetes groups. Our data point to changes in plasma levels of VEGF and its receptor sFlt-1 in diabetes and atherosclerosis that may have relevance for therapy and angiogenesis in these conditions.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Akihiko Sato ◽  
Akiomi Yoshihisa ◽  
Yuki Kanno ◽  
Mai Takiguchi ◽  
Shunsuke Miura ◽  
...  

Background: Although circulating levels of vascular endothelial growth factor (VEGF), known as a stimulator of angiogenesis, were elevated in peripheral artery disease (PAD), patients with PAD is often associated with poor collateral formation, resulting in critical limb ischemia. Recently, it has been reported that VEGF165b, a major splicing variant of human VEGF-A, inhibits angiogenesis in some types of cancer and acts as anti-angiogenic. However, the association between circulating levels of VEGF165b and clinical manifestation of patients with PAD has not been fully examined. Methods and Results: This study included 45 patients with PAD who received endovascular therapy and 20 control subjects without PAD in our hospital. PAD was diagnosed according to the PAD management guidelines, such as computed tomography, angiography, and/or ankle-brachial index. We excluded patients with malignancy, end-stage renal disease on dialysis, severe chronic respiratory failure, and active inflammatory disease in consideration of influence on concentrations of VEGF. We measured circulating concentrations of VEGF165b in peripheral blood samples using enzyme-linked immunosorbent assay (ELISA). Plasma levels of VEGF165b were significantly higher in the PAD group than in the control group (91.7 ± 47.8 pg/ml vs. 30.4 ± 18.3 pg/ml, P<0.001). There was no association between the plasma levels of VEGF165b and the symptom grade (Fontaine class), ankle-brachial index and the lesion morphology based on angiographical findings (TASC-II classification, presence of below knee lesion or chronic total occlusion lesion) in PAD group. In the multiple regression analysis, the independent factors to determine plasma levels of VEGF165b were age (ß 0.258, P=0.031), presence of PAD (ß 0.587, P<0.001), hypertension (ß 0.295, P=0.013), dyslipidemia (ß 0.385, P=0.001), history of stroke (ß 0.245, P=0.041), and coronary artery disease (ß 0.292, P=0.016). Conclusion: Plasma levels of VEGF165b was elevated in PAD, but there was no association between the severity of PAD and levels of VEGF165b. VEGF165b was related to age, hypertension, dyslipidemia, history of cerebral and coronary artery disease as well as PAD.


Author(s):  
Mohammad Alidoosti ◽  
Mehrnoosh Shanaki ◽  
Armita Mahdavi ◽  
Narges Mohammadtaghvaei

Background: The vascular endothelial growth factor (VEGF), as an angiogenic cytokine, binds endothelial cell receptors and stimulates angiogenesis and collateral formation. We evaluated the association between VEGF plasma levels and the gene polymorphism rs699947 and the formation of coronary collaterals in patients with coronary artery disease. Methods: A total of 195 patients with ≥70% narrowing in at least 1 coronary vessel (according to coronary angiography) were included in the study. The presence of the rs699947 polymorphism within the promoter of the VEGF gene was investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma VEGF concentration was quantified via the ELISA method. The Rentrop method was used to grade the extent of collateral development. Results: There was no significant difference in VEGF levels between the groups with good and poor collaterals. The frequency of the A allele of rs699947 was found to be higher in the patients with good collaterals than in those with poor collaterals (P=0.014). The odds ratio of good collaterals for AA was 2.67 (P=0.025) when compared with the CC genotype. Further, our additive model revealed an association between the rs699947 polymorphism and collateral formation (OR: 1.96, 95% CI: 1.05–3.65, P=0.033). Conclusion: The rs699947 polymorphism might be a novel genetic factor affecting collateral development in Iranian patients with coronary artery disease.


Angiology ◽  
2013 ◽  
Vol 65 (8) ◽  
pp. 683-690 ◽  
Author(s):  
Andrew W. Gardner ◽  
Donald E. Parker ◽  
Polly S. Montgomery ◽  
Danuta Sosnowska ◽  
Ana I. Casanegra ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document