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vascular smooth muscle cell and telomerase

Pan Tan, Yan-Jiao Wang, Shuang Li, Yi Wang, Je-Yu He, Yi-Yin Chen, Hui-Qian Deng, Wu Huang, Jun-Kun Zhan, You-Shuo Liu
Replicative senescence of vascular smooth muscle cells (VSMCs) contributes to aging as well as age-related cardiovascular diseases. Rapamycin can delay the onset of aging-related diseases via inhibition of the mammalian target of rapamycin (mTOR), but its role in vascular aging remains elusive. This study investigated the involvement of mTOR signaling in replicative senescence of VSMCs. Replicative senescence was induced by the extended passages of human VSMCs. Aging-related cell morphology was observed. The aging-related proteins and enzyme activity, and oxidative stress were measured...
November 2016: Molecular and Cellular Biochemistry
Timo Z Nazari-Shafti, John P Cooke
Cellular senescence of endothelial cells plays an important role in the development of vascular lesions that ultimately lead to an atherosclerotic plaque. This review focuses on the age-related changes of endothelial and vascular smooth muscle cells that contribute to vascular disease and discusses potential new targets that could rejuvenate the vascular system and thereby prevent or delay atherosclerosis.
July 2015: Methodist DeBakey Cardiovascular Journal
Ana Martín-Pardillos, Víctor Sorribas
Age-related effects of the vascular wall have been associated with several hemodynamic dysfunctions, including medial vascular calcification. Vascular aging has been traditionally addressed using proliferative senescence of vascular smooth muscle cells (VSMC) in vitro, which induces osteoblastic transition and favors calcification in vitro. In this work, we have analyzed the relationship between organismal aging and proliferative senescence by comparing the proliferative aging of VSMC obtained from young, mature, and old rats (2-, 12-, and 24-month cell lines [CL], respectively)...
November 2015: Physiological Reports
P Michael Grossman, Emile R Mohler, Blake J Roessler, Robert L Wilensky, Bruce L Levine, Edward Y Woo, Gilbert R Upchurch, Jacob Schneiderman, Belly Koren, Marina Hutoran, Diana Gershstein, Moshe Y Flugelman
UNLABELLED: Alternative treatment strategies for claudication are needed and cell-based therapies designed to induce angiogenesis are promising. The purpose of this report was to conduct a Phase I safety, dose-escalating, non-randomized, open-label study of autologous, fully differentiated venous endothelial and smooth muscle cells called MultiGeneAngio (MGA) for claudication due to peripheral artery disease. Twelve subjects, at two centers, received a single intra-arterial infusion of a suspension of equal amounts of transduced autologous venous smooth muscle cells expressing vascular endothelial growth factor (VEGF165) and endothelial cells expressing angiopoietin-1 (Ang-1) (Cohort 1: 1 × 10(7), Cohort 2: 2 × 10(7), Cohort 3: 5 × 10(7), Cohort 4: 7 × 10(7))...
February 2016: Vascular Medicine
Lei Lv, Yaxue Shi, Rundan Duan, Hui Xie, Jiwei Zhang, Wei Liang, Guanhua Xue, Lan Zhang, Xiaozhong Huang
Inhibition of intimal hyperplasia plays an important role in preventing restenosis. Previously, we reported the provocative role of Pin1 in regulating vascular smooth muscle cell (VSMC) proliferation. Here we intended to identify whether locally delivered lentivirus-mediated siPin1 via pluronic F127 (PF127) could inhibit neointimal formation and further explore the potential mechanisms thereof. In vitro studies revealed that lentivirus-mediated siPin1 dispersed in PF127 suppressed proliferation and induced senescence in VSMCs...
2015: Current Gene Therapy
Andrew R Mendelsohn, James W Larrick
Reduced telomere length with increasing age in dividing cells has been implicated in contributing to the pathologies of human aging, which include cardiovascular and metabolic disorders, through induction of cellular senescence. Telomere shortening results from the absence of telomerase, an enzyme required to maintain telomere length. Telomerase reverse transcriptase (TERT), the protein subunit of telomerase, is expressed only transiently in a subset of adult somatic cells, which include stem cells and smooth muscle cells...
October 2015: Rejuvenation Research
Nathalie Mouraret, Amal Houssaïni, Shariq Abid, Rozenn Quarck, Elisabeth Marcos, Aurelien Parpaleix, Guillaume Gary-Bobo, Jean-Luc Dubois-Randé, Geneviève Derumeaux, Jorge Boczkowski, Marion Delcroix, Maria A Blasco, Larissa Lipskaia, Valérie Amsellem, Serge Adnot
BACKGROUND: Cells exhibiting dysregulated growth may express telomerase reverse transcriptase (TERT), the dual function of which consists of maintaining telomere length, in association with the RNA template molecule TERC, and controlling cell growth. Here, we investigated lung TERT in human and experimental pulmonary hypertension (PH) and its role in controlling pulmonary artery smooth muscle cell (PA-SMC) proliferation. METHODS AND RESULTS: Marked TERT expression or activity was found in lungs from patients with idiopathic PH and from mice with PH induced by hypoxia or serotonin-transporter overexpression (SM22-5HTT(+) mice), chiefly within PA-SMCs...
February 24, 2015: Circulation
Nilank C Shah, Gatha J Shah, Zhiqiang Li, Xian-Cheng Jiang, Bella T Altura, Burton M Altura
1) short-term dietary deficiency of magnesium (Mg; 21 days) in rats (MgD) would result in a downregulation of telomerase in cardiac and aortic smooth muscle cells, 2) low levels of Mg(2+) added to drinking water (DW) would either prevent or greatly reduce the downregulation of telomerase in MgD, 3) MgD in rats would cause an upregulation of neutral-sphingomyelinase (N-SMAse) and p53, 4) short-term MgD would result in oxidation of DNA in diverse cardiac muscle and aortic smooth muscle cells as exemplified by measurement of 8-hydroxydeoxyguanosine (8-OH-dG), and 5) cross-talk between telomerase, N-SMase, p53, and 8-OH-dG would be evident in left ventricular (LV), right ventricular (RV), atrial and aortic smooth muscle obtained from rats subjected to short-term MgD...
2014: International Journal of Clinical and Experimental Medicine
Wei-Li Wang, Yi-Ting Yeh, Li-Jing Chen, Jeng-Jiann Chiu
Human telomerase reverse transcriptase (hTERT) and oncogene c-Myc have been shown to regulate cell proliferation. Our previous studies demonstrated that fibrillar collagen mediates vascular smooth muscle cell (SMC) cycle progression and proliferation in response to platelet-derived growth factor (PDGF)-BB and interleukin (IL)-1β. However, whether hTERT and c-Myc are involved in these fibrillar collagen-mediated SMC responses remain unclear. The present study elucidated the regulatory role of hTERT and c-Myc in PDGF-BB/IL-1β-induced cell cycle progression in SMCs on fibrillar collagen and its underlying mechanisms...
April 2014: Biomaterials
Tingting Shen, Jun Ma, Lei Zhang, Xiufeng Yu, Mengmeng Liu, Yunlong Hou, Yanyan Wang, Cui Ma, Shuzhen Li, Daling Zhu
OBJECTIVE: Pulmonary hypertension (PH) is characterized with pulmonary vasoconstriction and vascular remodeling mediated by 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) according to our previous studies. Meanwhile, telomerase reverse transcriptase (TERT) activity is highly correlated with vascular injury and remodeling, suggesting that TERT may be an essential determinant in the development of PH. The aim of this study was to determine the contribution and molecular mechanisms of TERT in the pathogenesis of PH...
2013: PloS One
Xiaodong Sun, Fang Han, Junling Yi, Ningning Hou, Zhibin Cao
Serious complications as a result of type 2 diabetes mellitus (T2DM) are becoming a major health concern. In the present study, it was hypothesized that telomerase activity is upregulated in vascular smooth muscle cells (VSMCs) during proliferation in T2DM and that the application of telomerase inhibitors impedes the proliferation of VSMCs in vitro. Male Wistar rats were randomly allocated into the normal control (NC) or diabetic (DM) group. Diabetes was induced by high‑fat feeding and a low dose of streptozotocin (STZ; 30 mg/kg)...
May 2013: Molecular Medicine Reports
Shiqin Xiong, Gloria Salazar, Nikolay Patrushev, Minhui Ma, Farshad Forouzandeh, Lula Hilenski, R Wayne Alexander
OBJECTIVE: Cellular senescence influences organismal aging and increases predisposition to age-related diseases, in particular cardiovascular disease, a leading cause of death and disability worldwide. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis and function, oxidative stress, and insulin resistance. Senescence is associated with telomere and mitochondrial dysfunction and oxidative stress, implying a potential causal role of PGC-1α in senescence pathogenesis...
May 2013: Arteriosclerosis, Thrombosis, and Vascular Biology
Zhenyu Tang, Aijun Wang, Falei Yuan, Zhiqiang Yan, Bo Liu, Julia S Chu, Jill A Helms, Song Li
It is generally accepted that the de-differentiation of smooth muscle cells, from the contractile to the proliferative/synthetic phenotype, has an important role during vascular remodelling and diseases. Here we provide evidence that challenges this theory. We identify a new type of stem cell in the blood vessel wall, named multipotent vascular stem cells. Multipotent vascular stem cells express markers, including Sox17, Sox10 and S100β, are cloneable, have telomerase activity, and can differentiate into neural cells and mesenchymal stem cell-like cells that subsequently differentiate into smooth muscle cells...
2012: Nature Communications
E R Parra, R Falzoni, V L Capelozzi
In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1) and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP) using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF). Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci), severe (mural) fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score...
July 2012: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Nicole Büchner, Niloofar Ale-Agha, Sascha Jakob, Ulrich Sydlik, Kerstin Kunze, Klaus Unfried, Joachim Altschmied, Judith Haendeler
Diet and pollution are environmental factors known to compromise "healthy aging" of the cardiovascular and respiratory systems. The molecular consequences of this permanent burden in these cells are still unknown. Therefore, this study investigates the impact of unhealthy diet on aging-related signaling pathways of human, primary cardiovascular cells and of airborne particles on lung epithelial and human endothelial cells. Nutrition health reports have shown that the diet in industrialized countries contains more than 100mg/dl low density lipoprotein (LDL) and a high fraction of added sugars, especially fructose...
January 2013: Experimental Gerontology
Fabiola Olivieri, Ilaria Mazzanti, Angela M Abbatecola, Rina Recchioni, Fiorella Marcheselli, Antonio D Procopio, Roberto Antonicelli
Statins are well established drugs for primary and secondary prevention of coronary artery disease (CAD). Despite the well-known ability of statins to lower cholesterol, it is now clear that clinical benefits are also substantially higher than expected and several clinical trials, like JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) have indicated that such clinical effects are independent of cholesterol reduction. These cholesterol-independent actions have been named "pleiotropic effects" and include: anti-oxidation and anti-inflammatory effects, modulation of immune activation, stabilization of atherosclerotic plaque, decreased platelet activation, inhibition of cardiac hypertrophy, reduction of cytokine-mediated vascular smooth muscle cell (VSMC) proliferation and improvement of endothelial function...
March 2012: Current Vascular Pharmacology
Jorge S Burns, Malthe Kristiansen, Lars P Kristensen, Kenneth H Larsen, Maria O Nielsen, Helle Christiansen, Jan Nehlin, Jens S Andersen, Moustapha Kassem
BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis...
2011: PloS One
De-xiu Bu, Maria E Johansson, Jingyi Ren, Da-wei Xu, F Brad Johnson, Kristina Edfeldt, Zhong-qun Yan
OBJECTIVE: To gain insights into mechanisms by which intimal hyperplasia interferes with the repair process by investigating expression and function of the catalytic telomerase reverse transcriptase (TERT) subunit after vascular injury. METHODS AND RESULTS: Functional telomerase is essential to the replicative longevity of vascular cells. We found that TERT was de novo activated in the intima of injured arteries, involving activation of the nuclear factor κB pathway...
December 2010: Arteriosclerosis, Thrombosis, and Vascular Biology
Pierre Charbord
This review describes the historical emergence of the concept of bone marrow mesenchymal stem cells (MSCs), summarizing data on Wolf and Trentin's hematopoietic inductive microenvironment; Dexter's hematopoiesis-supportive stromal cells; Friedenstein's osteogenic cells; and Pittenger's trilineal osteoblastic, chondrocytic, and adipocytic precursors; to finally introduce the specific bone marrow mesenchymal stem cells with differentiation potential to four lineages (mesenchymal and vascular smooth muscle lineages), and stromal and immunomodulatory capacities...
September 2010: Human Gene Therapy
Lucy Cassar, He Li, Fang-Xu Jiang, Jun-Ping Liu
Recent studies suggest that transforming growth factor beta (TGF-beta) inhibits telomerase activity by repression of the telomerase reverse transcriptase (TERT) gene. In this report, we show that TGF-beta induces TERT repression-dependent apoptosis in pancreatic tumor, vascular smooth muscle, and cervical cancer cell cultures. TGF-beta activates Smad3 signaling, induces TERT gene repression and results in G1/S phase cell cycle arrest and apoptosis. TERT over-expression stimulates the G1/S phase transition and alienates TGF-beta-induced cell cycle arrest and apoptosis...
May 14, 2010: Molecular and Cellular Endocrinology
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