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      Preventive effects of basic fibroblast growth factor on vascular restenosis after balloon angioplasty

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          Abstract

          The aim of the present study was to investigate whether chronic administration of basic fibroblast growth factor (bFGF) following angioplasty in a dog model of atherosclerotic iliac stenosis may restore endothelium function and prevent restenosis (RS). In total, 40 dogs with atherosclerotic stenosis of the right iliac arteries were used in the study. A total of 20 dogs underwent histological examination of the lumen areas prior to (n=10) and immediately following angioplasty (n=10). Intravenous bFGF was administered to 10 dogs (bFGF group) and an additional 10 dogs received vehicle injection (control group). Animals in the two groups were sacrificed 42 days following surgery for in vitro analysis of vascular reactivity and morphometric assessment of the histological cross-sectional areas. The bFGF group exhibited significantly greater maximal endothelium-dependent acetylcholine-induced relaxation (E max, 43±9%) when compared with the control group (E max, 8±6%; P<0.05). In addition, the maximal endothelium-independent response of the bFGF group to sodium nitroprusside (E max, 90±2%) was greater than that of the control group (E max, 60±2%; P<0.05). Six weeks following angioplasty, the lumen area in the bFGF group (2.01±0.78 mm 2) was greater compared with the control group (1.0±0.10%). The lumen area decreased by 58% between immediately after angioplasty and the control group six weeks following angioplasty. Therefore, the results of the present study indicated that administration of bFGF may not only restore endothelium-dependent and -independent relaxation, but also prevent RS in dogs that have undergone angioplasty.

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          Yap1 protein regulates vascular smooth muscle cell phenotypic switch by interaction with myocardin.

          The Hippo-Yap (Yes-associated protein) signaling pathway has emerged as one of the critical pathways regulating cell proliferation, differentiation, and apoptosis in response to environmental and developmental cues. However, Yap1 roles in vascular smooth muscle cell (VSMC) biology have not been investigated. VSMCs undergo phenotypic switch, a process characterized by decreased gene expression of VSMC contractile markers and increased proliferation, migration, and matrix synthesis. The goals of the present studies were to investigate the relationship between Yap1 and VSMC phenotypic switch and to determine the molecular mechanisms by which Yap1 affects this essential process in VSMC biology. Results demonstrated that the expression of Yap1 was rapidly up-regulated by stimulation with PDGF-BB (a known inducer of phenotypic switch in VSMCs) and in the injured vessel wall. Knockdown of Yap1 impaired VSMC proliferation in vitro and enhanced the expression of VSMC contractile genes as well by increasing serum response factor binding to CArG-containing regions of VSMC-specific contractile genes within intact chromatin. Conversely, the interaction between serum response factor and its co-activator myocardin was reduced by overexpression of Yap1 in a dose-dependent manner. Taken together, these results indicate that down-regulation of Yap1 promotes VSMC contractile phenotype by both up-regulating myocardin expression and promoting the association of the serum response factor-myocardin complex with VSMC contractile gene promoters and suggest that the Yap1 signaling pathway is a central regulator of phenotypic switch of VSMCs.
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            The adventitia: a progenitor cell niche for the vessel wall.

            Recent observations suggest that the adventitial layer of blood vessels exhibits properties resembling a stem/progenitor cell niche. Progenitor cells have been isolated from the adventitia of both murine and human blood vessels with the potential to form endothelial cells, mural cells, osteogenic cells, and adipocytes. These progenitors appear to cluster at or near the border zone between the outer media and inner adventitia. In the mouse, this border zone region corresponds to a localized site of sonic hedgehog signaling in the artery wall. This brief review will discuss the emerging evidence that the tunica adventitia may provide a niche-like signaling environment for resident progenitor cells and will address the role of the adventitia in growth, remodeling, and repair of the artery wall. Copyright © 2011 S. Karger AG, Basel.
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              Physical training increases eNOS vascular expression and activity and reduces restenosis after balloon angioplasty or arterial stenting in rats.

              The effects of dynamic exercise on restenosis after vascular injury are still unknown. The consequences of balloon dilation-induced injury on neointimal hyperplasia, vascular negative remodeling, and reendothelialization were assessed in sedentary and trained rats. Ex vivo eNOS vascular expression and activity were investigated in carotid arteries isolated from sedentary and exercised rats. The in vivo effects of eNOS inhibition by L-NMMA on vessel wall after balloon dilation were evaluated in sedentary and exercised rats. We also investigated the effects of exercise on neointimal formation in a rat stent model of vascular injury. Compared with sedentary group, the arteries isolated from trained rats showed higher levels of eNOS protein expression and activity 7 days after balloon dilation. A significant reduction of both neointimal hyperplasia and negative remodeling was observed 14 days after balloon injury in trained compared with sedentary rats. Moreover, we demonstrated that exercise training produced accelerated reendothelialization of the balloon injured arterial segments compared with sedentary. L-NMMA administration eliminated the benefits of physical training on vessel wall after balloon dilation. Finally, a decrease of neointimal hyperplasia as well as of platelet aggregation was observed after stent deployment in trained rats compared with sedentary. In conclusion, physical exercise could favorably affect restenosis after balloon angioplasty and stenting. Increase in eNOS expression and activity might contribute to the potential beneficial effects of exercise on the vessel wall after vascular injury.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                May 2014
                19 February 2014
                19 February 2014
                : 7
                : 5
                : 1193-1196
                Affiliations
                Department of Vascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
                Author notes
                Correspondence to: Dr Changjian Liu, Department of Vascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, P.R. China, E-mail: frandoc@ 123456163.com
                Article
                etm-07-05-1193
                10.3892/etm.2014.1562
                3991498
                24940410
                6fbe393f-e6d1-460b-8f17-7712a1acceba
                Copyright © 2014, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 09 September 2013
                : 29 January 2014
                Categories
                Articles

                Medicine
                basic fibroblast growth factor,angioplasty,vascular endothelium
                Medicine
                basic fibroblast growth factor, angioplasty, vascular endothelium

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