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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.11 P.948-956

http://doi.org/10.1631/jzus.B1500076


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


Author(s):  Rados?aw Wieczr, Gra?yna Gadomska, Barbara Ruszkowska-Ciastek, Katarzyna Stankowska, Jacek Budzy?ski, Jacek Fabisiak, Karol Suppan, Grzegorz Pulkowski, Danuta Ro??

Affiliation(s):  Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toru?, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland; more

Corresponding email(s):   wieczorcmumk@tlen.pl

Key Words:  Angiogenesis, Peripheral arterial disease, Soluble receptors, Type 2 diabetes mellitus, Vascular endothelial growth factor


Rados?aw Wieczr, Gra?yna Gadomska, Barbara Ruszkowska-Ciastek, Katarzyna Stankowska, Jacek Budzy?ski, Jacek Fabisiak, Karol Suppan, Grzegorz Pulkowski, Danuta Ro??. 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[J]. Journal of Zhejiang University Science B, 2015, 16(11): 948-956.

@article{title="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",
author="Rados?aw Wieczr, Gra?yna Gadomska, Barbara Ruszkowska-Ciastek, Katarzyna Stankowska, Jacek Budzy?ski, Jacek Fabisiak, Karol Suppan, Grzegorz Pulkowski, Danuta Ro??",
journal="Journal of Zhejiang University Science B",
volume="16",
number="11",
pages="948-956",
year="2015",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1500076"
}

%0 Journal Article
%T 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
%A Rados?aw Wieczr
%A Gra?yna Gadomska
%A Barbara Ruszkowska-Ciastek
%A Katarzyna Stankowska
%A Jacek Budzy?ski
%A Jacek Fabisiak
%A Karol Suppan
%A Grzegorz Pulkowski
%A Danuta Ro??
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 11
%P 948-956
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500076

TY - JOUR
T1 - 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
A1 - Rados?aw Wieczr
A1 - Gra?yna Gadomska
A1 - Barbara Ruszkowska-Ciastek
A1 - Katarzyna Stankowska
A1 - Jacek Budzy?ski
A1 - Jacek Fabisiak
A1 - Karol Suppan
A1 - Grzegorz Pulkowski
A1 - Danuta Ro??
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 11
SP - 948
EP - 956
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500076


Abstract: 
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=0.000 007 and P=0.000 000 1, respectively) and significantly lower sVEGFR-2 levels (P=0.02 and P=0.000 01, 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 angiogenesis 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.

2型糖尿病对外周动脉疾病患者血浆内的血管内皮生长因子及其可溶性受体浓度的影响

目的:研究2型糖尿病对外周动脉疾病患者血浆内的血管内皮生长因子(VEGF-A)及其水溶性受体(sVEGFR-1和sVEGFR-2)浓度的影响。
创新点:首次研究了2型糖尿病对外周动脉疾病患者血浆内sVEGFR-1和sVEGFR-2浓度的影响。
方法:选取46个外周动脉疾病患者,根据有无2型糖尿病分为糖尿病组(15例)和无糖尿病组(31例),另选30个健康志愿者为正常对照组。采用酶联免疫吸附法(ELISA)检测他们血浆中VEGF-A及sVEGFR-1和sVEGFR-2的浓度,然后通过对比各组浓度研究2型糖尿病的影响。
结论:与正常对照组相比,外周动脉疾病患者具有较高的VEGF-A浓度(2型糖尿病组P=0.000 007,非糖尿病组P=0.000 000 1)以及较低的sVEGFR-2浓度(2型糖尿病组P=0.02,非糖尿病组P=0.000 01)。同时,2型糖尿病组比非糖尿病组具有较低的VEGF-A浓度及较高的sVEGFR-1和sVEGFR-2浓度。研究结果表明:无论2型糖尿病是否共存,缺氧是导致血管生成的一个关键的刺激因素;同时,高血糖状态对下肢的血管生成有抑制作用。

关键词:血管生成;外周动脉疾病;可溶性受体;2型糖尿病;血管内皮生长因子

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Aref, S., El Sherbiny, M., Goda, T., et al., 2005. Soluble VEGF/sFLt1 ratio is an independent predictor of AML patient outcome. Hematology, 10(2):131-134.

[2]Bao, P., Kodra, A., Tomic-Canic, M., et al., 2009. The role of vascular endothelial growth factor in wound healing. J. Surg. Res., 153(2):347-358.

[3]Blann, A.D., Belgore, F.M., McCollum, C.N., et al., 2002. Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or Type II diabetes. Clin. Sci., 102: 187-194.

[4]Bleda, S., de Haro, J., Varela, C., et al., 2012. Impact of VEGF polymorphisms on the severity of peripheral artery disease in diabetic patients. Growth Factors, 30(5):277-282.

[5]Botti, C., Maione, C., Dogliotti, G., et al., 2012. Circulating cytokines present in the serum of peripheral arterial disease patients induce endothelial dysfunction. J. Biol. Regul. Homeost. Agents, 26(1):67-79.

[6]Chang, Y.T., Chang, M.C., Wei, S.C., et al., 2008. Serum vascular endothelial growth factor/soluble vascular endothelial growth factor receptor 1 ratio is an independent prognostic marker in pancreatic cancer. Pancreas, 37(2):145-150.

[7]Chung, A.W., Hsiang, Y.N., Matzke, L.A., et al., 2006. Reduced expression of vascular endothelial growth factor paralleded with the increased angiostatin expression resulting from the upregulated activities matrix metalloproteinase-2 and -9 in human type 2 diabetic arterial vasculature. Circ. Res., 99(2):140-148.

[8]Drela, E., Kulwas, A., Jundziłł, A., et al., 2014. VEGF-A and PDGF-BB—angiogenic factors and the stage of diabetic foot syndrome advancement. Endokrynol. Pol., 65(4):306-312.

[9]Duh, E., Aiello, L.P., 1999. Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox. Diabetes, 48(10):1899-1906.

[10]Fadini, G.P., Miorin, M., Facco, M., et al., 2005. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J. Am. Coll. Cardiol., 45(9):1449-1457.

[11]Hazarika, S., Dokun, A.O., Li, Y., et al., 2007. Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1. Circ. Res., 101(9):948-956.

[12]Hochberg, I., Hoffman, A., Levy, A.P., 2001. Regulation of VEGF in diabetic patients with critical limb ischemia. Ann. Vasc. Surg., 15(3):388-392.

[13]Jude, E.B., Eleftheriadou, I., Tentolouris, N., 2010. Peripheral arterial disease in diabetes—a review. Diabetes Med., 27(1):4-14.

[14]Kusumanto, Y.H., van Weel, V., Mulder, N.H., et al., 2006. Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial. Hum. Gene Ther., 17(6):683-691.

[15]Libra, M., Signorelli, S.S., Bevelacqua, Y., et al., 2006. Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease. J. Clin. Pathol., 59(2):211-215.

[16]Lim, H.S., Lip, G.Y., Blann, A.D., 2005. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis, 180(1):113-118.

[17]Liu, W., Zhang, X., Song, C., et al., 2014. Expression and characterization of a soluble VEGF receptor 2 protein. Cell Biosci., 4(1):14.

[18]Meyer, R.D., Mohammadi, M., Rahimi, N., 2006. A single amino acid substitution in the activation loop defines the decoy characteristic of VEGFR-1/FLT-1. J. Biol. Biochem., 281(2):867-875.

[19]Norgren, L., Hiatt, W.R., Dormandy, J.A., et al., 2007. Inter-society consensus for the management of peripheral arterial disease (TASC II). Eur. J. Vasc. Endovasc. Surg., 33(Suppl. 1):S1-S75.

[20]Orrico, C., Pasquinelli, G., Foroni, L., et al., 2010. Dysfunctional vasa vasorum in diabetic peripheral artery obstructive disease with critical lower limb ischaemia. Eur. J. Vasc. Endovasc. Surg., 40(3):365-374.

[21]Rość, D., Wieczór, R., Stankowska, K., et al., 2014. Plasma VEGF-A/SVEGFR-1 ratio as a potential ischemic marker in patients with symptomatic peripheral arterial disease— preliminary report. Thromb. Res., 133(Suppl. 3):95.

[22]Ruszkowska-Ciastek, B., Sokup, A., Socha, M.W., et al., 2014. A preliminary evaluation of VEGF-A, VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 15(6):575-581.

[23]Skóra, J., Barć, P., Pupka, A., et al., 2013. Transplantation of autologous bone marrow mononuclear cells with VEGF gene improves diabetic critical limb ischaemia. Endokrynol. Pol., 64(2):129-138.

[24]Toi, M., Bando, H., Ogawa, T., et al., 2002. Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int. J. Cancer, 98(1):14-18.

[25]Waltenberger, J., Lange, J., Kranz, A., 2000. Vascular endothelial growth factor-A induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: a potential predictor for the individual capacity to develop collaterals. Circulation, 102(2):185-190.

[26]Yamaguchi, T., Bando, H., Mori, T., et al., 2007. Overexpression of soluble vascular endothelial growth factor receptor 1 in colorectal cancer: association with progression and prognosis. Cancer Sci., 98(3):405-410.

[27]Zakareia, F.A., 2012. Correlation of peripheral arterial blood flow with plasma chemerin and VEGF in diabetic peripheral vascular disease. Biomark. Med., 6(1):81-87.

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