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Coexistence of proangiogenic potential and increased MMP-9, TIMP-1, and TIMP-2 levels in the plasma of patients with critical limb ischemia

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第8期20卷 687-692页

作者： Radoslaw Wieczór Anna Maria Wieczór Arleta Kulwas grzegorz pulkowski Jacek Budzyński Danuta Rosc Department of Pathophysiology Faculty of Pharmacy Nicolaus Copernicus University in Toruń Ludwik Rydygier Collegium Medicum in Bydgoszcz Bydgoszcz PL 85-094 Poland Clinic of Vascular and Internal Medicine Dr Jan Biziel University Hospital No. 2 in Bydgoszcz Bydgoszcz PL 85-168 Poland Department of Vascular and Internal Medicine Faculty of Health Sciences Nicolaus Copernicus University in Toruń Ludwik Rydygier Collegium Medicum in Bydgoszcz Bydgoszcz PL 85-168 Poland

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.

关键词：严重肢体缺血间歇性跛行血管内皮生长因子金属蛋白酶

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Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2016年第11期17卷 842-849页

作者： Radoslaw WIECZóR Anna Maria WIECZóR Grazyna GADOMSKA Katarzyna STANKOWSKA Jacek FABISIAK Karol SUPPAN grzegorz pulkowski Jacek BUDZYNSKI Danuta ROSC Department of Pathophysiology Faculty of PharmacyNicolaus Copernicus University in ToruhLudwik Rydygier Collegium Medicum in BydgoszczBydgoszcz PL 85-094Poland Clinic of Vascular and Internal Medicine Dr.Jan Biziel University Hospital No.2 in BydgoszezBydgoszcz PL 85-168Poland Department of Vascular and Internal Medicine Faculty of Health SciencesNicolaus Copernicus University in ToruhLudwik Rydygier Collegium Medicum in BydgoszezBydgoszcz PL 85-168Poland

Objective： Being overweight or obese comprises a significant risk factor for atherosclerosis. Fat tissue also generates factors stimulating angiogenesis, the process by which new blood vessels form. The purpose of this paper is to assess concentrations of the vascular endothelial growth factor A （VEGF-A） and its soluble type-1 and type-2 re- ceptors （sVEGFR-1 and sVEGFR-2） in plasma of patients with peripheral arterial disease （PAD） depending on the level of nutrition according to body mass index （BMI）. Methods： The study group included patients suffering from symptomatic PAD （n=46） in Fontaine classes Ila-lV without any history of neoplastic disease and who have a normal BMI （n=15）, are overweight （n=21） or are obese （n=10）. The control group （n=30） consisted of healthy non-smoking volunteers who were neither overweight nor obese. Venous blood plasma samples were collected from both groups at rest in the morning to determine plasma concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 using the enzyme- linked immunosorbent assay （ELISA） method. Results： The group of patients with PAD co-existent with being over- weight or obese tended to have higher mean concentration levels of VEGF-A and sVEGFR-2 when compared with patients suffering from PAD with normal BMIo A statistically significant positive correlation was obtained between BMI and average plasma concentrations of sVEGFR-2 （R=0.37, P=-0.0103）. However, no significant correlation was no- ticed between BMI and VEGF-A or sVEGFR-1 concentrations. Conclusions： A positive correlation determined be- tween the level of antiangiogenic factor and BMI value may be indicative of the linearly growing prevalence of some antiangiogenic factors in patients with metabolic disorders, which may be one of numerous factors contributing to incomplete efficiency of collateral circulation development in patients with PAD.

关键词： Overweight Obesity Angiogenesis Vascular endothelial growth factor Soluble type-1 and type-2receptors Peripheral arterial disease

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Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第11期16卷 948-956页

作者： Rados?aw WIECZóR Gra?yna GADOMSKA Barbara RUSZKOWSKA-CIASTEK Katarzyna STANKOWSKA Jacek BUDZY?SKI Jacek FABISIAK Karol SUPPAN grzegorz pulkowski Danuta RO?? Department of Pathophysiology Faculty of Pharmacy Nicolaus Copernicus University in ToruńLudwik Rydygier Collegium Medicum in Bydgoszcz Clinic of Vascular and Internal Medicine Dr.Jan Biziel University Hospital No.2 in Bydgoszcz Department of Vascular and Internal Medicine Faculty of Health Sciences Nicolaus Copernicus University in ToruńLudwik Rydygier Collegium Medicum in Bydgoszcz

Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis-the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor （vascular endothelial growth factor A （VEGF-A）） and angiogenesis inhibitors （soluble VEGF receptors type 1 and type 2 （sVEGFR-1 and sVEGFR-2）） in patients with PAD. Methods： Among 46 patients with PAD under pharmacological therapy （non-invasive）, we identified, based on medical history, a subgroup with coexistent type 2 diabetes （PAD-DM2＋, n=15） and without diabetes （PAD-DM2-, n=31）. The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Results： The subgroups of PAD-DM2＋ and PAD-DM2- revealed significantly higher concentrations of VEGF-A （P=-0.000007 and P=0.0000001, respectively） and significantly lower sVEGFR-2 levels （P=-0.02 and P=-0.00001, respectively）, when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions： The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor （VEGF-A） and higher levels of anglogenesis inhibitors （sVEGFR-1 and sVEGFR-2） at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.

关键词： Angiogenesis Peripheral arterial disease Soluble receptors Type 2 diabetes mellitus Vascular endothelialgrowth factor

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