Curcumin induces therapeutic angiogenesis in a diabetic mouse hindlimb ischemia model via modulating the function of endothelial progenitor cellsReportar como inadecuado

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Stem Cell Research and Therapy

, 8:182

First Online: 03 August 2017Received: 14 March 2017Revised: 22 June 2017Accepted: 21 July 2017


BackgroundNeovascularization is impaired in diabetes mellitus, which leads to the development of peripheral arterial disease and is mainly attributed to the dysfunction of endothelial progenitor cells EPCs. Previous studies proved the promotional effect of curcumin on neovascularization in wound healing of diabetes. Thus, we hypothesize that curcumin could promote neovascularization at sites of hindlimb ischemia in diabetes and might take effect via modulating the function of EPCs.

MethodsStreptozotocin-induced type 1 diabetic mice and nondiabetic mice both received unilateral hindlimb ischemic surgery. Curcumin was then administrated to the mice by lavage for 14 days consecutively. Laser Doppler perfusion imaging was conducted to demonstrate the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. In addition, angiogenesis, migration, proliferation abilities, and senescence were determined in EPCs isolated from diabetic and nondiabetic mice. Quantitative PCR was then used to determine the mRNA expression of vascular endothelial growth factor VEGF and angiopoetin-1 Ang-1 in EPCs.

ResultsCurcumin application to type 1 diabetic mice significantly improved blood reperfusion and increased the capillary density in ischemic hindlimbs. The in-vitro study also revealed that the angiogenesis, migration, and proliferation abilities of EPCs and the number of senescent EPCs were reversed by curcumin application. Quantitative PCR confirmed the overexpression of VEGF-A and Ang-1 in EPCs after curcumin treatment.

ConclusionCurcumin could enhance neovascularization via promoting the function of EPCs in a diabetic mouse hindlimb ischemia model.

KeywordsCurcumin Diabetes mellitus Endothelial progenitor cells Hindlimb ischemia Neovascularization AbbreviationsAng-1Angioprotein-1

BMBone marrow

BM-MNCBone marrow mononuclear cell

DMDiabetes mellitus

EPCEndothelial progenitor cell

HPFHigh-power field

LDPILaser Doppler perfusion imaging

PADPeripheral arterial disease

SDStandard deviation

VEGFVascular endothelial growth factor

Electronic supplementary materialThe online version of this article doi:10.1186-s13287-017-0636-9 contains supplementary material, which is available to authorized users.

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Autor: Jinzhi You - Jiacheng Sun - Teng Ma - Ziying Yang - Xu Wang - Zhiwei Zhang - Jingjing Li - Longgang Wang - Masaaki Ii - J


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