https://scholars.lib.ntu.edu.tw/handle/123456789/384339
標題: | MK-0626, a dipeptidyl peptidase-4 inhibitor, improves neovascularization by increasing both the number of circulating endothelial progenitor cells and endothelial nitric oxide synthetase expression | 作者: | Shih, C.-M. SHINN-CHIH WUet al. |
關鍵字: | Dipeptidyl peptidase-4; Endothelial nitric oxide synthase; Endothelial progenitor cells; Stromal cell-derived factor-1 | 公開日期: | 2014 | 卷: | 21 | 期: | 17 | 起(迄)頁: | 2012-2022 | 來源出版物: | Current Medicinal Chemistry | 摘要: | Current treatment modalities for critical limb ischemia (CLI) are of limited benefit; therefore, advances in therapeutic vasculogenesis may open an important new avenue for the treatment of CLI. This study examines the therapeutic potential of the DPP-4 inhibitor MK-0626 as a regulator of vasculogenesis in vivo. MK-0626 was administered daily to C57CL/B6 mice and eGFP-labeled bone marrow-transplanted ICR mice that had undergone hind limb ischemia surgery. Laser Doppler imaging and flow cytometry were used to evaluate the degree of neo-vasculogenesis and the number of circulating endothelial progenitor cells (EPCs), respectively. Cell surface markers of EPCs and the level of endothelial nitric oxide synthase (eNOS) were studied in the vessels. Mice that received MK-0626 had an elevated level of glucagon- like peptide-1 (GLP-1) and a decreased level of dipeptidyl peptidase-4 (DPP-4) in their plasma, in addition to an ischemia-induced increase in the level of stromal cell-derived factor-1 (SDF-1). In C57CL/B6 mice, blood flow in the ischemic limb was significantly improved by treatment with MK-0626. The number of circulating EPCs and both the synthesis and phosphorylation of eNOS were also increased in ischemic thigh muscle after MK-0626 treatment. In contrast, similar effects of MK-0626 were not observed in B6.129P2-Nos3tm1Unc/J mice (an eNOS knockout mouse). Additionally, MK-0626 treatment promoted the mobilization and homing of EPCs to ischemic tissue in eGFP transgenic mouse bone marrow-transplanted ICR mice. We conclude that both the number of circulating EPCs and neo-vasculogenesis are increased in response to DPP-4 inhibitor treatment and that this occurs via an eNOS-dependent mechanism. The results highlight the therapeutic vasculogenesis potential of the DPP-4 inhibitor MK-0626 using a hind limb ischemia mouse model. ? 2014 Bentham Science Publishers. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84899872989&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/384339 |
DOI: | 10.2174/09298673113206660273 | SDG/關鍵字: | cell surface marker; dipeptidyl peptidase IV; dipeptidyl peptidase IV inhibitor; endothelial nitric oxide synthase; glucagon like peptide 1; mk 0626; stromal cell derived factor 1; unclassified drug; dipeptidyl peptidase IV; dipeptidyl peptidase IV inhibitor; endothelial nitric oxide synthase; MK0626; stromal cell derived factor 1; triazole derivative; angiogenesis; animal experiment; animal model; article; bone marrow transplantation; capillary density; cell homing; cell motility; controlled study; critical limb ischemia; drug safety; endothelial progenitor cell; flow cytometry; in vivo study; laser Doppler flowmetry; limb blood flow; male; mouse; nonhuman; protein phosphorylation; thigh; angiogenesis; animal; C57BL mouse; drug effects; endothelial progenitor cell; Institute for Cancer Research mouse; ischemia; limb; metabolism; pathology; vascularization; Animals; Bone Marrow Transplantation; Chemokine CXCL12; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Endothelial Progenitor Cells; Extremities; Ischemia; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Neovascularization, Physiologic; Nitric Oxide Synthase Type III; Triazoles |
顯示於: | 動物科學技術學系 |
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