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vascular smooth muscle cell plasticity

Brittany G Durgin, Adam C Straub
Vascular smooth muscle cells (SMC) play a major role in vascular diseases, such as atherosclerosis and hypertension. It has long been established in vitro that contractile SMC can phenotypically switch to function as proliferative and/or migratory cells in response to stimulation by oxidative stress, growth factors, and inflammatory cytokines. Reactive oxygen species (ROS) are oxidative stressors implicated in driving vascular diseases, shifting cell bioenergetics, and increasing SMC proliferation, migration, and apoptosis...
February 20, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Rhian M Touyz, Rheure Alves-Lopes, Francisco J Rios, Livia L Camargo, Aikaterini Anagnostopoulou, Anders Arner, Augusto C Montezano
Hypertension is a major risk factor for many common chronic diseases, such as heart failure, myocardial infarction, stroke, vascular dementia and chronic kidney disease. Pathophysiological mechanisms contributing to the development of hypertension include increased vascular resistance, determined in large part by reduced vascular diameter due to increased vascular contraction and arterial remodelling. These processes are regulated by complex interacting systems such as the renin angiotensin aldosterone system (RAAS), sympathetic nervous system, immune activation and oxidative stress, which influence vascular smooth muscle function...
January 31, 2018: Cardiovascular Research
Kurt R Stenmark, Maria G Frid, Brian B Graham, Rubin M Tuder
Pulmonary hypertension (PH) is the end result of interaction between pulmonary vascular tone and a complex series of cellular and molecular events termed "vascular remodeling". The remodeling process, which can involve the entirety of pulmonary arterial vasculature, almost universally involves medial thickening, driven by increased numbers and hypertrophy of its principal cellular constituent, smooth muscle cells (SMCs). It is noted, however that SMCs comprise heterogeneous populations of cells, which can exhibit markedly different proliferative, inflammatory, and extracellular matrix production changes during remodeling...
January 27, 2018: Cardiovascular Research
Nicholas J Leeper, Lars Maegdefessel
The vascular smooth muscle cell (SMC) is one of the most plastic cells in the body. Understanding how non-coding RNAs regulate SMC cell-fate decision making in the vasculature has significantly enhanced our understanding of disease development, and opened up exciting new avenues for potential therapeutic applications. Recent studies on SMC physiology have in addition challenged our traditional view on their role and contribution to vascular disease, mainly in the setting of atherosclerosis as well as aneurysm disease, and restenosis after angioplasties...
December 29, 2017: Cardiovascular Research
Mei Fen Shih, Kuang-Hung Pan, Chia-Chyuan Liu, Chia-Rui Shen, Jong Yuh Cherng
The initiation of atherosclerosis involves up-regulation of molecules such as E-selectin, VCAM-1, and ICAM-1. The progression of atherosclerosis is linked to proliferation and migration of vascular smooth muscle cell via MMP-2 and MMP-9 activities. However, the etiology of atherosclerosis concerning plasticizers is unknown. We evaluated β-thujaplicin in preventing the development of atherosclerosis in a model induced by pro-inflammatory cytokines. Moreover, we established a new atherosclerosis model in vascular smooth muscle cells (VSMC) exposed to a common contact plasticizer, di(2-ethylhexyl)phthalate (DEHP)...
December 27, 2017: Regulatory Toxicology and Pharmacology: RTP
Melissa Mariana, Joana Feiteiro, Elisa Cairrao
Phthalates are one of the main constituents of plastic, reaching up to 40% of the total plastic weight, and their main function is to impart flexibility/elasticity to polymers that would otherwise be rigid. Phthalates are known as endocrine disruptors, since they can interfere with hormone homeostasis. Regarding the cardiovascular system, it was already shown the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure with significant changes in several calcium-handling proteins and an increase in the blood pressure of mice offspring, suggesting that DEHP leads to vasocontraction...
December 8, 2017: Cardiovascular Toxicology
Salli Antila, Sinem Karaman, Harri Nurmi, Mikko Airavaara, Merja H Voutilainen, Thomas Mathivet, Dmitri Chilov, Zhilin Li, Tapani Koppinen, Jun-Hee Park, Shentong Fang, Aleksanteri Aspelund, Mart Saarma, Anne Eichmann, Jean-Léon Thomas, Kari Alitalo
The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect...
December 4, 2017: Journal of Experimental Medicine
Patrick Lacolley, Véronique Regnault, Patrick Segers, Stéphane Laurent
The cushioning function of large arteries encompasses distension during systole and recoil during diastole which transforms pulsatile flow into a steady flow in the microcirculation. Arterial stiffness, the inverse of distensibility, has been implicated in various etiologies of chronic common and monogenic cardiovascular diseases and is a major cause of morbidity and mortality globally. The first components that contribute to arterial stiffening are extracellular matrix (ECM) proteins that support the mechanical load, while the second important components are vascular smooth muscle cells (VSMCs), which not only regulate actomyosin interactions for contraction but mediate also mechanotransduction in cell-ECM homeostasis...
October 1, 2017: Physiological Reviews
Ivar von Kügelgen
P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. The platelet ADP-receptor which has been denominated P2Y12 receptor is an important target in pharmacotherapy. The receptor couples to Gαi2 mediating an inhibition of cyclic AMP accumulation and additional downstream events including the activation of phosphatidylinositol-3-kinase and Rap1b proteins. The nucleoside analogue ticagrelor and active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel block P2Y12 receptors and, thereby, inhibit ADP-induced platelet aggregation...
September 12, 2017: Advances in Experimental Medicine and Biology
Meera Murgai, Wei Ju, Matthew Eason, Jessica Kline, Daniel W Beury, Sabina Kaczanowska, Markku M Miettinen, Michael Kruhlak, Haiyan Lei, Jack F Shern, Olga A Cherepanova, Gary K Owens, Rosandra N Kaplan
A deeper understanding of the metastatic process is required for the development of new therapies that improve patient survival. Metastatic tumor cell growth and survival in distant organs is facilitated by the formation of a pre-metastatic niche that is composed of hematopoietic cells, stromal cells and extracellular matrix (ECM). Perivascular cells, including vascular smooth muscle cells (vSMCs) and pericytes, are involved in new vessel formation and in promoting stem cell maintenance and proliferation. Given the well-described plasticity of perivascular cells, we hypothesized that perivascular cells similarly regulate tumor cell fate at metastatic sites...
October 2017: Nature Medicine
Benoit Langlois, Ekaterina Belozertseva, Ara Parlakian, Mustapha Bourhim, Jacqueline Gao-Li, Jocelyne Blanc, Lei Tian, Dario Coletti, Carlos Labat, Zhor Ramdame-Cherif, Pascal Challande, Véronique Regnault, Patrick Lacolley, Li Zhenlin
Intermediate filaments are involved in stress-related cell mechanical properties and in plasticity via the regulation of focal adhesions (FAs) and the actomyosin network. We investigated whether vimentin regulates endothelial cells (ECs) and vascular smooth muscle cells (SMCs) and thereby influences vasomotor tone and arterial stiffness. Vimentin knockout mice (Vim(-/-)) exhibited increased expression of laminin, fibronectin, perlecan, collagen IV and VE-cadherin as well as von Willebrand factor deposition in the subendothelial basement membrane...
September 14, 2017: Scientific Reports
Marina Cardano, Giuseppe R Diaferia, Luciano Conti, Simona Baronchelli, Alessandro Sessa, Vania Broccoli, Andrea Barbieri, Pasquale De Blasio, Ida Biunno
mSEL-1L is a highly conserved ER-resident type I protein, involved in the degradation of misfolded peptides through the ubiquitin-proteasome system (UPS), a pathway known to control the plasticity of the vascular smooth muscle cells (VSMC) phenotype and survival. In this article, we demonstrate that mSEL-1L deficiency interferes with the murine embryonic vascular network, showing particular irregularities in the intracranic and intersomitic neurovascular units and in the cerebral capillary microcirculation...
August 17, 2017: Journal of Cellular Physiology
Chunlian Peng, Siming Zhang, Haixin Liu, Yanxiao Jiao, Guifa Su, Yan Zhu
Vascular Smooth muscle cells (VSMCs) possess remarkable phenotype plasticity that allows it to rapidly adapt to fluctuating environmental cues, including the period of development and progression of vascular diseases such as atherosclerosis and restenosis subsequent to vein grafting or coronary intervention. Although VSMC phenotypic switch is an attractive target, there is no effective drug so far. Using rat aortic VSMCs, we investigate the effects of Ligustrazine and its synthetic derivatives on platelet-derived growth factor-BB (PDGF-BB) induced proliferation and phenotypic switch by a cell image-based screening of 60 Ligustrazine stilbene derivatives...
November 5, 2017: European Journal of Pharmacology
Xuechong Hong, Andriana Margariti, Alexandra Le Bras, Laureen Jacquet, Wei Kong, Yanhua Hu, Qingbo Xu
Endothelial dysfunction is widely implicated in cardiovascular pathological changes and development of vascular disease. In view of the fact that the spontaneous endothelial cell (EC) regeneration is a slow and insufficient process, it is of great interest to explore alternative cell sources capable of generating functional ECs. Vascular smooth muscle cell (SMC) composes the majority of the vascular wall and retains phenotypic plasticity in response to various stimuli. The aim of this study is to test the feasibility of the conversion of SMC into functional EC through the use of reprogramming factors...
July 17, 2017: Scientific Reports
Anna Huhtinen, Vesa Hongisto, Asta Laiho, Eliisa Löyttyniemi, Dirk Pijnenburg, Mika Scheinin
BACKGROUND: α2-adrenoceptors are important regulators of vascular tone and blood pressure. Regulation of cell proliferation is a less well investigated consequence of α2-adrenoceptor activation. We have previously shown that α2B-adrenoceptor activation stimulates proliferation of vascular smooth muscle cells (VSMCs). This may be important for blood vessel development and plasticity and for the pathology and therapeutics of cardiovascular disorders. The underlying cellular mechanisms have remained mostly unknown...
June 28, 2017: BMC Systems Biology
Marie-José Goumans, Peter Ten Dijke
Genetic studies in animals and humans indicate that gene mutations that functionally perturb transforming growth factor β (TGF-β) signaling are linked to specific hereditary vascular syndromes, including Osler-Rendu-Weber disease or hereditary hemorrhagic telangiectasia and Marfan syndrome. Disturbed TGF-β signaling can also cause nonhereditary disorders like atherosclerosis and cardiac fibrosis. Accordingly, cell culture studies using endothelial cells or smooth muscle cells (SMCs), cultured alone or together in two- or three-dimensional cell culture assays, on plastic or embedded in matrix, have shown that TGF-β has a pivotal effect on endothelial and SMC proliferation, differentiation, migration, tube formation, and sprouting...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
Paul Hindle, Nusrat Khan, Leela Biant, Bruno Péault
Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have demonstrated increased chondrogenic potential compared with those from subcutaneous fat. This research assessed the chondrogenic potential of IFP PSCs compared with MSCs from the IFP and bone marrow...
January 2017: Stem Cells Translational Medicine
Nuno Guimarães-Camboa, Paola Cattaneo, Yunfu Sun, Thomas Moore-Morris, Yusu Gu, Nancy D Dalton, Edward Rockenstein, Eliezer Masliah, Kirk L Peterson, William B Stallcup, Ju Chen, Sylvia M Evans
Pericytes are widely believed to function as mesenchymal stem cells (MSCs), multipotent tissue-resident progenitors with great potential for regenerative medicine. Cultured pericytes isolated from distinct tissues can differentiate into multiple cell types in vitro or following transplantation in vivo. However, the cell fate plasticity of endogenous pericytes in vivo remains unclear. Here, we show that the transcription factor Tbx18 selectively marks pericytes and vascular smooth muscle cells in multiple organs of adult mouse...
March 2, 2017: Cell Stem Cell
Khandaker Ahtesham Ahmed, Tianli Zhang, Katsuhiko Ono, Hiroyasu Tsutsuki, Tomoaki Ida, Soichiro Akashi, Keishi Miyata, Yuichi Oike, Takaaki Akaike, Tomohiro Sawa
Guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinases (PKG) are kinases regulating diverse physiological functions including vascular smooth muscle relaxation, neuronal synaptic plasticity, and platelet activities. Certain PKG inhibitors, such as Rp-diastereomers of derivatives of guanosine 3',5'-cyclic monophosphorothioate (Rp-cGMPS), have been designed and used to study PKG-regulated cell signaling. 8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is an endogenous cGMP derivative formed as a result of excess production of reactive oxygen species and nitric oxide...
March 1, 2017: Biological & Pharmaceutical Bulletin
Tomomi Natori, Masachika Fujiyoshi, Masashi Uchida, Natsuki Abe, Tatsuro Kanaki, Yasunori Fukumoto, Itsuko Ishii
The proliferation of vascular smooth muscle cells (SMCs) causes restenosis in biomaterial vascular grafts. The purposes of this study were to establish a suspension culture system for SMCs by using a novel substrate, low-acyl gellan gum (GG) and to maintain SMCs in a state of growth inhibition. When SMCs were cultured in suspension with GG, their proliferation was inhibited. Their viability was 70% at day 2, which was maintained at more than 50% until day 5. In contrast, the viability of cells cultured in suspension without GG was 5...
March 2017: In Vitro Cellular & Developmental Biology. Animal
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