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

Wieczór, Radosław; Gadomska, Grażyna; Ruszkowska-Ciastek, Barbara; Stankowska, Katarzyna; Budzyński, Jacek; Fabisiak, Jacek; Suppan, Karol; Pulkowski, Grzegorz; Rość, Danuta

doi:10.1631/jzus.b1500076

Cited by 17 publications

(12 citation statements)

References 26 publications

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“…This is the result of reduced blood flow through affected arterial vessels. Such observations can be found in relevant available publications (Findley et al, 2008;Stehr et al, 2010) and our own surveys (Wieczór et al, 2015a;2015b). Nevertheless, the present study relied on assessing the possible effect of weight-related disorders on angiogenesis parameters in patients suffering from PAD.…”

Section: Discussionsupporting

confidence: 66%

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

Wieczór

Gadomska

et al. 2016

J. Zhejiang Univ. Sci. B

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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 receptors (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 IIa-IV 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 enzymelinked immunosorbent assay (ELISA) method. Results: The group of patients with PAD co-existent with being overweight or obese tended to have higher mean concentration levels of VEGF-A and sVEGFR-2 when compared with patients suffering from PAD with normal BMI. 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 noticed between BMI and VEGF-A or sVEGFR-1 concentrations. Conclusions: A positive correlation determined between 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.

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Section: Discussionsupporting

confidence: 66%

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

Wieczór

Gadomska

et al. 2016

J. Zhejiang Univ. Sci. B

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“…Elevated sFlt-1 was found to be involved in the development of macroangiopathic and microangiopathic diseases since this factor acts as a VEGF antagonist by making them unavailable for signaling to membrane-bound receptors, thereby leading to dysfunction of endothelium [ 1 – 3 ]. Wieczor et al [ 4 ] found that sFlt-1 production in T2DM patients complicated with peripheral arterial disease was higher than that in nondiabetic individuals with peripheral arterial disease. Lappas [ 5 ] demonstrated that adipose tissue was a major source of elevated sFlt-1 levels in obesity and GDM.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated that elevated circulating soluble vascular endothelial growth factor (VEGF) receptor 1, also called soluble fms-like tyrosine kinase-1 (sFlt-1), is one of the major contributors to the development of macroangiopathic and microangiopathic diseases, such as ischaemic heart disease, chronic kidney disease, and preeclampsia [ 1 – 3 ]. Wieczor et al's study has demonstrated that the production of sFlt-1 is significantly upregulated in type 2 diabetes mellitus (T2DM) patients with peripheral arterial disease [ 4 ]. In obesity and gestational diabetes mellitus (GDM), adipose tissue, rather than placental tissue, is thought to be the main source of elevated sFlt-1 levels [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Inhibits High Glucose-Induced sFlt-1 Production via Decreasing ADAM17 Expression in 3T3-L1 Adipocytes

Wang

et al. 2017

International Journal of Endocrinology

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Hydrogen sulfide (H 2 S) has recently been identified as an endogenous gaseous signaling molecule. The aim of the present study was to investigate the effect of H 2 S on high glucose-(HG-) induced ADAM17 expression and sFlt-1 production in 3T3-L1 adipocytes. Firstly, we found that HG DMEM upregulated the expression of ADAM17 and production of sFlt-1 in 3T3-L1 adipocytes. Knocking down ADAM17 attenuated the effect of high glucose on sFlt-1 production in adipocytes. HG decreased the expression of CSE and 3-MST, as well as the endogenous H 2 S production. Furthermore, knocking down CSE and 3-MST significantly increased ADAM17 expression and sFlt-1 production. The addition of exogenous H 2 S through the administration of sodium hydrosulfide (NaHS) inhibited HG-induced upregulation of ADAM17 expression and sFlt-1 production. In conclusion, decreased expression of CSE and 3-MST and the subsequent decrease in H 2 S production contribute to high glucose-induced sFlt-1 production via activating ADAM17 in adipocytes. Exogenous H 2 S donor NaHS has a potential therapeutic value for diabetic vascular complications.

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“…Therefore, the altered collateral vessel formation in diabetic PAD might be attributed to defects in downstream signal transduction rather than in VEGF production in response to ischemia ( 13 , 14 ). This hypothesis is further supported by increased levels of both soluble vascular endothelial growth factor receptor 1 (sVEGFR1) and 2 (sVEGFR2) in the serum of T2D patients with PAD compared with nondiabetic PAD individuals ( 21 ) that could act as decoys to sequestrate VEGF-A ( 15 ). Collectively, the lack of significant improvement of the PAD following exogenous administration of VEGF could be attributed to decreased local bioavailability and unresponsiveness of VEGF in diabetic individuals.…”

Section: Deregulation Of Pro-angiogenic Factors In Diabetic Padmentioning

confidence: 93%

“…As a result of blunted cellular response to hypoxia, hypoxia-inducible factor-1 alpha (HIF-1α) itself and most of its target genes, including VEGF, are reduced in a diabetic state ( 29 ). Thus, a slightly lower non-significant expression of VEGF-A was observed in the serum of type 2 diabetic (T2D) PAD patients compared with non-diabetic PAD individuals ( 21 ). On the other hand, PAD is characterized by a tremendously favorable ischemic environment triggering VEGF production and an ample number of investigations have suggested that patients with PAD and coexisting diabetes display higher or at least unchanged serum levels of VEGF-A ( Table 1 ) ( 13 – 20 , 22 – 25 ).…”

Section: Deregulation Of Pro-angiogenic Factors In Diabetic Padmentioning

confidence: 95%

Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease

Mercier

Rousseau

Geraldes

2021

Front. Cardiovasc. Med.

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Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.

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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

Cited by 17 publications

References 26 publications

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

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

Hydrogen Sulfide Inhibits High Glucose-Induced sFlt-1 Production via Decreasing ADAM17 Expression in 3T3-L1 Adipocytes

Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease

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