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vascular smooth muscle cell senescence

Elizabeth B Endorf, Hua Qing, Jun Aono, Naoto Terami, Geneviève Doyon, Eric Hyzny, Karrie L Jones, Hannes M Findeisen, Dennis Bruemmer
OBJECTIVE: Aberrant proliferation of smooth muscle cells (SMC) in response to injury induces pathological vascular remodeling during atherosclerosis and neointima formation. Telomerase is rate limiting for tissue renewal and cell replication; however, the physiological role of telomerase in vascular diseases remains to be determined. The goal of the present study was to determine whether telomerase reverse transcriptase (TERT) affects proliferative vascular remodeling and to define the molecular mechanism by which TERT supports SMC proliferation...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD(+)-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways...
October 15, 2016: Aging
S G Li, M Z Yan, D Zhang, M Ye, J J Deng
The development of age-related cardiovascular disease is associated with the senescence of vascular cells. This study aimed to investigate the effect of ginsenoside Rg1 on vascular smooth muscle cell (VSMC) senescence. Primary VSMCs were cultured and divided into control, D-galactose (D-gal), Rg1-L, and Rg1-H groups, which were cultured without and with D-gal, and with low- and high-concentrations of Rg1, respectively. D-gal-induced cellular senescence was identified by b-galactosidase staining, and ultrastructural changes within the cells were observed...
September 2, 2016: Genetics and Molecular Research: GMR
Giuseppe Maltese, Paraskevi-Maria Psefteli, Benedetta Rizzo, Salil Srivastava, Luigi Gnudi, Giovanni E Mann, Richard C M Siow
Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated...
October 3, 2016: Journal of Cellular and Molecular Medicine
Hou-Zao Chen, Fang Wang, Peng Gao, Jian-Fei Pei, Yue Liu, Ting-Ting Xu, Xiaoqiang Tang, Wen-Yan Fu, Jie Lu, Yun-Fei Yan, Xiao-Man Wang, Lei Han, Zhu-Qin Zhang, Ran Zhang, Ming-Hui Zou, De-Pei Liu
RATIONALE: Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with advancing age in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown. OBJECTIVE: In this study, we investigated the role of SIRT1 (Sirtuin 1), a class III histone deacetylase, in AAA formation and the underlying mechanisms linking vascular senescence and inflammation...
October 28, 2016: Circulation Research
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
Rafaela G Feresin, Jingwen Huang, DawnKylee S Klarich, Yitong Zhao, Shirin Pourafshar, Bahram H Arjmandi, Gloria Salazar
Activation of angiotensin II (Ang II) signaling during aging increases reactive oxygen species (ROS) leading to vascular senescence, a process linked to the onset and progression of cardiovascular diseases (CVD). Consumption of fruits and vegetables, particularly berries, is associated with decreased incidence of CVD, which has mainly been attributed to the polyphenol content of these foods. Thus, the objective of this study was to investigate the role of blackberry (BL), raspberry (RB), and black raspberry (BRB) polyphenol extracts in attenuating Ang II-induced senescence in vascular smooth muscle cells (VSMCs) and to determine the molecular mechanisms involved...
October 12, 2016: Food & Function
Meili Wang, Yi Fu, Cheng Gao, Yiting Jia, Yaqian Huang, Limei Liu, Xian Wang, Wengong Wang, Wei Kong
Aging-related vascular dysfunction contributes to cardiovascular morbidity and mortality. Cartilage oligomeric matrix protein (COMP), a vascular extracellular matrix protein, has been described as a negative regulatory factor for the vascular aging-related processes including atherosclerosis and vascular calcification. However, whether COMP is implicated in the process of vascular aging remains unclear. Here, we identified a novel function of COMP in preventing vascular aging and vascular smooth muscle cells (VSMCs) senescence...
September 16, 2016: Biochemical and Biophysical Research Communications
Tengfei Zhou, Mengqian Zhang, Liang Zhao, Aiqin Li, Xiaomei Qin
Oxidative stress and impaired antioxidant defense are believed to be contributors to the cardiovascular aging process. The transcription factor nuclear factor-E2-related factor 2 (Nrf2) plays a key role in orchestrating cellular antioxidant defenses and maintaining redox homeostasis. Our previous study showed that Exendin-4, a glucagon-like peptide-1 analog, alleviates angiotensin II (ANG II)-induced vascular smooth muscle cell (VSMC) senescence by inhibiting Rac1 activation via cAMP/PKA (Zhao L, Li AQ, Zhou TF, Zhang MQ, Qin XM...
October 1, 2016: American Journal of Physiology. Cell Physiology
Mirna Saker, Larissa Lipskaia, Elisabeth Marcos, Shariq Abid, Aurelien Parpaleix, Amal Houssaini, Pierre Validire, Philippe Girard, Hiba Noureddine, Laurent Boyer, Nora Vienney, Valerie Amsellem, Laurent Marguerit, Bernard Maitre, Geneviève Derumeaux, Jean-Luc Dubois-Rande, Claude Jourdan-Lesaux, Marion Delcroix, Rozenn Quarck, Serge Adnot
OBJECTIVE: Senescent pulmonary artery smooth muscle cells (PA-SMCs) may contribute to the pathogenesis of pulmonary hypertension by producing secreted factors. The aim of this study was to explore the role in pulmonary hypertension of extracellular matrix proteins released by senescent PA-SMCs. APPROACH AND RESULTS: Polymerase chain reaction array analysis of human PA-SMCs undergoing replicative senescence revealed osteopontin upregulation, which mediated the stimulatory effect of senescent PA-SMC media and matrix on PA-SMC growth and migration...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Sumaya Dauleh, Ilaria Santeramo, Claire Fielding, Kelly Ward, Anne Herrmann, Patricia Murray, Bettina Wilm
The human omentum has been long regarded as a healing patch, used by surgeons for its ability to immunomodulate, repair and vascularise injured tissues. A major component of the omentum are mesothelial cells, which display some of the characteristics of mesenchymal stem/stromal cells. For instance, lineage tracing studies have shown that mesothelial cells give rise to adipocytes and vascular smooth muscle cells, and human and rat mesothelial cells have been shown to differentiate into osteoblast- and adipocyte-like cells in vitro, indicating that they have considerable plasticity...
2016: PloS One
Ya Gao, Juan Peng, Zhong Ren, Ni-Ya He, Qing Li, Xue-Shan Zhao, Mei-Mei Wang, Hong-Yan Wen, Zhi-Han Tang, Zhi-Sheng Jiang, Gui-Xue Wang, Lu-Shan Liu
MicroRNAs are a group of endogenously small non-coding RNA molecules that downregulate gene expression at the post-transcriptional level through binding to the 3'UTR of target mRNAs. Recent findings have revealed a key role for microRNAs in the pathophysiological processes of atherosclerosis. As a complex disease, atherosclerosis is influenced by a combination of multiple genes and environmental factors. Both of them play a role in atherogenesis by affecting different types of cells (such as endothelial cell, vascular smooth muscle cell and monocyte/macrophage) function...
September 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
I-Ching Tsai, Zih-Cian Pan, Hui-Pin Cheng, Chen-Hsiu Liu, Bor-Tyng Lin, Meei Jyh Jiang
Cellular senescence has emerged as an important player in both physiology and pathology. Excessive reactive oxygen species (ROS) is known to mediate cellular senescence. NADPH oxidases are major sources for ROS production in the vascular wall; the roles of different NADPH oxidase isoforms in cellular senescence remain unclear, however. We investigated the roles of two NADPH oxidase isoforms in mitochondrial dysfunction during angiotensin II (Ang II)-induced cellular senescence of human aortic vascular smooth muscle cells (VSMCs)...
September 2016: Journal of Molecular and Cellular Cardiology
Dong-Jie Li, Fang Huang, Min Ni, Hui Fu, Liang-Sheng Zhang, Fu-Ming Shen
OBJECTIVE: α7 nicotinic acetylcholine receptor (α7nAChR) is a subtype of nAChR and has been reported to be involved in hypertension end-organ damage. In this study, we tested the role of α7nAChR in angiotensin II (Ang II)-induced senescence of vascular smooth muscle cells (VSMCs). APPROACH AND RESULTS: Expression of α7nAChR was not influenced by Ang II. Ang II induced remarkable senescent phenotypes in rodent and human VSMCs, including increased senescence-associated β-galactosidase activity, phosphorylation of H2A...
August 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Bo Bai, Andy W C Man, Kangmin Yang, Yumeng Guo, Cheng Xu, Hung-Fat Tse, Weiping Han, Maria Bloksgaard, Jo G R De Mey, Paul M Vanhoutte, Aimin Xu, Yu Wang
Aims-SIRT1 exerts potent activity against cellular senescence and vascular ageing. By decreasing LKB1 protein levels, it promotes the survival and regeneration of endothelial cells. The present study aims to investigate the molecular mechanisms underlying SIRT1-mediated LKB1 degradation for the prevention of vascular ageing.Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells...
June 28, 2016: Oncotarget
Sabina Licholai, Michal Blaż, Boguslaw Kapelak, Marek Sanak
BACKGROUND: Complex etiopathogenesis of ascending aortic aneurysm suggests contribution of epigenetic mechanisms in its development. Several studies appointed microRNAs (miRs) as essential epigenetic factors in various human diseases; however, little is known about their role in ascending aortic aneurysm. Therefore, the aim of this study was to perform unbiased molecular screening of miRs expression in aneurysmal tissue and establish their functions on a transcriptional level. METHODS: Samples of ascending aortic tissue were obtained from 15 patients, and total RNA was isolated separately from aneurysmal and unaffected aortic tissue obtained from the same patient...
October 2016: Annals of Thoracic Surgery
Yan-qing Chen, Jing Zhao, Cheng-wei Jin, Yi-hui Li, Meng-xiong Tang, Zhi-hao Wang, Wei Zhang, Yun Zhang, Li Li, Ming Zhong
Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression...
June 2016: Age (2005-)
Hao Yin, J Geoffrey Pickering
Cellular senescence is a definable fate of cells within aging, diseased, and remodelling tissues. The traditional hallmark of cellular senescence is permanent cell cycle arrest but the senescent state is also accompanied by secretion of proteins that can reinforce the senescent phenotype and adversely affect the local tissue environment. Assessment for cellular markers of senescence has revealed the existence of senescent smooth muscle cells and senescent endothelial cells in vessels of patients with atherosclerosis and hypertension...
May 2016: Canadian Journal of Cardiology
Wioleta Grabowska, Małgorzata Suszek, Maciej Wnuk, Anna Lewinska, Emilia Wasiak, Ewa Sikora, Anna Bielak-Zmijewska
It is believed that curcumin, a component of the turmeric that belongs to hormetins, possesses anti-aging propensity. This property of curcumin can be partially explained by its influence on the level of sirtuins. Previously, we have shown that relatively high (2.5-10 µM) doses of curcumin induce senescence of cancer cells and cells building the vasculature. In the present study we examined whether curcumin at low doses (0.1 and 1 µM) is able to delay cell senescence and upregulate the level of sirtuins in human cells building the vasculature, namely vascular smooth muscle (VSMC) and endothelial (EC) cells...
April 12, 2016: Oncotarget
Yujiro Kida, Michael S Goligorsky
The sirtuins (SIRTs) constitute a class of proteins with nicotinamide adenine dinucleotide-dependent deacetylase or adenosine diphosphate-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors...
May 2016: Canadian Journal of Cardiology
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