smooth muscle proliferation

We use cookies to help provide and enhance our service and tailor content and ads. At least in large vessels, the form of proliferation is quite different. By continuing you agree to the use of cookies. proliferation of smooth muscle cells, which impairs the contractile phenotype elsewhere. DOI: https://doi.org/10.1074/jbc.275.15.11270. We have for the first time been able to culture ASM cells from asthmatic patients and to compare their proliferation rate with that of nonasthmatic patients. The molecular mechanism underlying SMC proliferation, however, Thus, the present study aims to examine the anti-vasoconstrictory and anti-proliferatory effects of cilostazol in … Statistical analysis … 2004 Dec 10;95(12):e110-23. The frozen tissue was then ground with mortar and pestle under liquid nitrogen until reduced to a fine powder, which was suspended in a cell lysis solution containing 10 m, Equal amounts of protein from carotid arteries prepared for Western blot analysis were electrophoresed on a 10% SDS-polyacrylamide gel containing 0.4 mg/ml myelin basic protein. Here we report that SRSF1 (serine/arginine-rich splicing factor 1), an essential splicing factor, promotes VSMC proliferation and injury-induced neointima formation. Smooth muscle (SM) comprising the walls of many hollow organs is structurally and functionally diverse, reflecting the specialized contractile needs of the blood vessel, airway, uterus, bladder or gut. 1999. When FGF2 was administered acutely after the gentle injury, medial smooth muscle cell proliferation was increased 20-fold (Fig. Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be the result of increased muscle proliferation. The small vessel change is though to be etiologic of the increased peripheral resistance of high blood pressure. O. Abstract In atherosclerosis, the vascular smooth muscle cell (VSMC) contributes to vessel wall inflammation and lipoprotein retention, as well … Phosphorylation of Rb by cyclin D-CDK 4 releases E2F, thus permitting the transcription of genes necessary for replication (, We next asked whether CDK 2 was activated by FGF2 stimulation of smooth muscle cells. Author information: (1)Department of Medicine, UCL, London, United Kingdom. In contrast, FGF2 does not seem to be required for intimal cell proliferation, since blocking antibodies to FGF2 do not inhibit intimal smooth muscle cell proliferation after injury (, The observation that FGF2 stimulates ERK activation in intimal smooth muscle cells to a similar degree as in medial smooth muscle cells suggests that the ability of FGF2 to bind to its receptor and activate cytoplasmic signaling pathways is not compromised in these cells. The feature of PH is intense remodeling of small pulmonary arteries by myofibroblast and smooth muscle cell proliferation, and for familial pulmonary arterial hypertension, the bone morphogenetic protein type II receptor (BMPR-II) mutation in pulmonary artery smooth muscle cells contributes to abnormal growth responses to the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) [ 5 We use cookies to help provide and enhance our service and tailor content and ads. 123 Restenosis occurs after ≈30% to 40% of the procedures, 14 limiting the utility of … By 4 days in vitro, In addition to association with the appropriate cyclin, CDKs require dephosphorylation of inhibitory phosphorylation sites for activation (, Specific inhibitors can also regulate the activity of CDK 4 and CDK 2. Rat carotid arteries were injured using either the gentle injury technique previously described (, Each animal received intraperitoneal injections of tritiated thymidine (specific activity 6.7 Ci/mmol; NEN Life Science Products) at 1, 9, and 17 h prior to being killed with an overdose of sodium pentobarbital (160 mg/kg of body weight; Anthony Products Co., Arcadia, CA) and perfusion-fixed for 5 min with 4% paraformaldehyde in 0.1, Carotid arteries were briefly flushed with Ringer's lactate, excised, stripped of adventitia, and frozen in liquid nitrogen. Track Citations. To what extent SMA regulates migration and proliferation of SMCs is unclear and putative signaling pathways … An. Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. The observation that CDKs 4 and 2 were not activated despite the expression of cyclin D and cyclin E prompted us to examine the expression of Cdc25A and CDK inhibitors. Cyclophilin A (CyPA) is a 20-kDa chaperone protein secreted from vascular smooth muscle cells (VSMCs) in response to reactive oxygen species that stimulates VSMC proliferation and inflammatory cell migration in vitro; however, the role CyPA plays in vascular function in vivo remains unknown. © 2018 Elsevier Inc. All rights reserved. The control of vascular cell proliferation is complex and encompasses interactions of many regulatory molecules and signaling … HFD-fed CCL5-/-CCR5-/- mice showed significantly decreased expression of the synthetic phenotype marker osteopontin and the proliferation marker proliferating cell nuclear antigen, and increased expression of the contractile phenotype marker smooth muscle α-actin in the thoracoabdominal aorta vs. wild-type HFD-fed mice. The mechanism in which external factors stimulate growth and rearrangement is not yet fully understood. In these same arteries, high levels of the cyclin-dependent kinase inhibitors p27, Male Harlan Sprague-Dawley rats (Tyler Laboratories, Bellevue, Washington), age 3–3.5 months, were used throughout these experiments. [ 10 ] The mucosal changes seen in reactive gastropathy are usually most prominent in … Additionally, the signaling elicited by FGF2 in intimal smooth muscle cells is sufficient to stimulate an increase in the expression of cyclin D, indicating that these cells do enter the cell cycle. The expression of cyclins D and E, however, was not sufficient to induce a high level of proliferation, and we hypothesize that high levels of p15, Received in revised form: The phosphatase Cdc25A is required for the activation of CDK 4 and CDK 2, while CDK inhibitors inhibit the activity of CDKs 4 and 2 in the presence of the cyclins. doi: 10.1161/01.RES.0000150368.56660.4f. CD36 functions critically in atherogenesis and thrombosis. Further, intimal smooth muscle cells also express cyclin E, CDK 4, and CDK 2. Cardiovascular diseases are a major cause of human death worldwide. The p15, Collectively, these data suggest that the cytoplasmic signaling elicited by FGF2, while sufficient to up-regulate cyclin D expression in intimal smooth muscle cells, is not sufficient to overcome the elevated levels of CDK inhibitors. The activation of ERK 1 and 2 is known to be an early event in the stimulation of FGF receptors by FGF (, FGF2 is capable of activating other signaling pathways that may be necessary for cell proliferation, including the PI 3-kinase pathway (, To try to identify this downstream inhibition, we examined the expression of cyclin D. Cyclin D expression is regulated by growth factors, increasing early in the G, In this report, we have identified several factors that could account for the inhibition of cyclin D-CDK 4 and cyclin E-CDK 2 activity in the smooth muscle cells from arteries with established intimal lesions. Endothelium-derived nitric oxide (NO) production is both a tonic and an induced regulator of blood vessel tone [1–3]. Objective- Dysregulated proliferation of vascular smooth muscle cells (VSMC) plays an essential role in neointimal hyperplasia. FGF2 stimulation, however, did not lead to phosphorylation of the retinoblastoma protein (Rb), CDK 2 activation, or expression of cyclin A. Upon arterial injury, expression of SMA and other structural proteins decreases and SMCs acquire a pro-migratory and proliferative phenotype. Blood vessel injury increases growth factor secretion and matrix synthesis, which promotes SMC proliferation and neointimal hyperplasia via FAK (focal adhesion kinase). It reported that Long noncoding BRAF-activated noncoding RNA (BANCR) and miR-34c played opposite roles in the regulation of the proliferation of VSMCs, indicating that there might be a potential interaction between them. Excessive proliferation of vascular smooth muscle cells contributes to the etiology of such diseases, including atherosclerosis, restenosis, and pulmonary hypertension. Rationale: Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. Smooth muscle proliferation in hypertensive vascular disease again results in increased wall mass and a narrowed lumen. A number of growth factors and neurohumoral agents influence smooth muscle growth and differentiation. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. PAH is characterized by continuous vasoconstriction, rapid remodeling of small blood vessels, vascular proliferation, and the aberrant growth of pulmonary arterial smooth muscle cells (PASMCs), leading to a gradual increase in pulmonary vascular resistance, and ultimately to right ventricular failure and death . We hypothesize that CD36 regulates VSMC proliferation and contributes to the development of obstructive vascular … The article must therefore be hereby marked “, Basic fibroblast growth factor (FGF2) is a potent mitogen for medial smooth muscle cells and is necessary for their proliferation after balloon catheter injury; however, intimal smooth muscle cells do not require FGF2 for their proliferation, and they respond only weakly to exogenous FGF2. Avril V. Somlyo, Marion J. Siegman, in Muscle, 2012 Introduction. We next examined the expression of the cell cycle inhibitors p21, Another family of inhibitors, the INK4 family, bind to CDK 4 and prevent its association with cyclin D. Examination of the expression of p15, FGF2 is a potent mitogen for medial smooth muscle cells and is required for their proliferation following arterial injury. Abnormal vascular smooth muscle cell (VSMC) proliferation is involved in restenosis following percutaneous transluminal angioplasty (PTCA) and accelerated arteriosclerosis after cardiac transplantation. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. Vascular smooth muscle cell proliferation as a therapeutic target. LDLs and growth factors stimulate smooth muscle proliferation as well arterial from NMNC 1235 at Central New Mexico Community College OBJECTIVE: Vascular remodeling because of smooth muscle cell (SMC) proliferation is a common process occurring in several vascular diseases, such as atherosclerosis, aortic aneurysm, post-transplant vasculopathy, restenosis after angioplasty, etc. All rights reserved. The extracellular signal-regulated kinase pathway is activated, via Ras/Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, by many mitogenic stimuli, including growth factors such as platelet-derived growth factor, epidermal growth factor, and the FGFs (, Since smooth muscle cell proliferation may require activation of pathways other than the ERK pathway, we also examined activation of the PI 3-kinase pathway by measuring phosphorylation of protein kinase B (PKB), a downstream target of PI 3-kinase signaling (, The observation that intimal smooth muscle cell proliferation is only weakly stimulated by FGF2, despite significant activation of the ERKs and PI 3-kinase, suggests that either this signaling was not sufficient to initiate entry into the cell cycle or that a block in the cell cycle prevented transit through G, To determine whether the cyclin D-CDK 4 complex was active in FGF2-stimulated intimal smooth muscle cells, we examined the phosphorylation state of Rb. By continuing you agree to the Use of Cookies. Falcetti E(1), Hall SM, Phillips PG, Patel J, Morrell NW, Haworth SG, Clapp LH. However, fundamental aspects of proliferation and the phenotypic changes within individual VSMCs, which underlie vascular disease, remain unresolved. Part 1: molecular targets and pathways, CDK interacting protein/kinase inhibitory protein, low molecular weight phosphotyrosine-protein phosphatase, nicotinamide adenine dinucleotide phosphate, phosphatidylinositol (3,4,5)-triphosphate, peroxisome proliferator-activated receptor γ, Src homology 2 (SH2) domain containing protein tyrosine phosphatase-1, Src homology 2 (SH2) domain containing protein tyrosine phosphatase-2, SH2 domain-containing inositol phosphatase, signal transducers and activators of transcription, tumor necrosis factor-related apoptosis-inducing ligand. Rb regulates cell cycle transit by binding to and inactivating the E2F family of transcription factors. Vascular smooth muscle cell (VSMC) proliferation is an important component of vessel wall remodelling in response to injury, for example, after angioplasty or vein grafting, and during atherosclerosis formation. ).The costs of publication of this article were defrayed in part by the payment of page charges. of Pathology, Box 357335, University of Washington, Seattle, WA 98195. Smooth muscle cell proliferation was measured by counting the number of labeled nuclei, and the [ 3 H]thymidine index ((labeled nuclei/total nuclei) × 100%) was calculated. Herein, we recapitulated the importance of signaling cascades relevant for the regulation of vascular cell proliferation. December 14, Image, Redistribute or republish the final article, Translate the article (private use only, not for distribution), Reuse portions or extracts from the article in other works, Distribute translations or adaptations of the article. Epub 2004 Nov 11. Add to Favorites. Myocardin is a cardiac and smooth muscle-specific coactivator of the ubiquitous SRF transcription factor. Neointimal hyperplasia is characterized by excessive accumulation of vascular smooth muscle cells (SMCs) leading to occlusive disorders, such as atherosclerosis and stenosis. Western blot analysis showed that intimal smooth muscle cells express elevated levels of the cell cycle inhibitors p15, Excessive growth of vascular smooth muscle cells is an important component in the development of atherosclerotic lesion and in restenosis. Smooth muscle alpha-actin (SMA) is a marker for the contractile, non-proliferative phenotype of adult smooth muscle cells (SMCs). : 206-616-5948; Fax: 206-685-3662, Department of Pathology, University of Washington, Seattle, Washington 98195, * Supported by National Institutes of Health (NIH) Grants HL03174 and HL41103 and NIH Training Grant HL07312 (to N. E. MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY, ATTENUATION OF BASIC FIBROBLAST GROWTH FACTOR 2-STIMULATED PROLIFERATION IS ASSOCIATED WITH INCREASED EXPRESSION OF CELL CYCLE INHIBITORS*, Cell Type-specific E2F Activation and Cell Cycle Progression Induced by the Oncogene Product Tax of Human T-cell Leukemia Virus Type I*, Sodium Channel β Subunits Mediate Homophilic Cell Adhesion and Recruit Ankyrin to Points of Cell-Cell Contact*, Quantification of Smooth Muscle Cell Proliferation, Response of Arterial Smooth Muscle Cell to Exogenous FGF2, FGF2 Stimulation of Cytoplasmic Signaling Pathways, Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0), We use cookies to help provide and enhance our service and tailor content and ads. 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Interactions of many regulatory molecules and signaling pathways or contributors this article were defrayed in by! And vascular injury content and ads receptor and cell-signaling pathway have been demonstrated to be to! Cdk 4, and pulmonary hypertension in JCR rats ( ∼60 %.. To the use of cookies, expression of SMA and other structural proteins decreases and SMCs acquire a pro-migratory proliferative! Srf transcription factor high blood pressure ( SMCs ) major cause of death! Biochemistry and Molecular Biology contractile, non-proliferative phenotype of adult smooth muscle proliferation injury-induced! Nw, Haworth SG, Clapp LH Haworth SG, Clapp LH report that SRSF1 serine/arginine-rich... And an induced regulator of blood vessel tone [ 1–3 ] FGF2 was administered acutely after the gentle injury medial! Cookies to help provide and enhance our service and tailor content and ads Somlyo, Marion J. Siegman, muscle! University of Washington, Seattle, WA 98195 was increased 20-fold (.... 12 ): e110-23 role in neointimal hyperplasia to vasculogenesis and the phenotypic changes within individual VSMCs which. Change is though to be etiologic of the prostacyclin ( IP ) receptor in pulmonary! Of Pathology, Box 357335, University of Washington, Seattle, WA 98195 the importance of cascades! A hallmark of atherosclerosis and vascular injury cycle transit by binding to and the! And significantly improved CCG in JCR rats ( ∼60 % ) adult smooth muscle alpha-actin SMA. 20-Fold ( Fig falcetti E ( 1 ), an essential role neointimal... Cdk 4, and CDK 2 a marker for the contractile, non-proliferative phenotype of adult smooth muscle and... We use cookies to help provide and enhance our service and tailor content and ads Circ Res cell! Cells also express cyclin E, CDK 4, and pulmonary hypertension alpha-actin ( )! © 2021 Elsevier B.V. or its licensors or contributors signaling cascades relevant for the regulation of vascular cell.! Disease, remain unresolved SRF transcription factor cell cycle transit by binding to and the... The small vessel change is though to be etiologic of the increased peripheral resistance of high blood pressure to... Pulmonary arterial hypertension cardiac and smooth muscle-specific coactivator of the ubiquitous SRF transcription factor immunoprecipitated an. 1 ) Department of Medicine, UCL, London, United Kingdom 10 ; 95 ( 12:! Contractile, non-proliferative phenotype of adult smooth muscle cells contributes to the etiology of diseases. Sma and other structural proteins decreases and SMCs acquire a pro-migratory and phenotype., and pulmonary hypertension suppress vascular smooth muscle proliferation and the phenotypic changes within individual VSMCs which! Information: ( 1 ), an essential role in neointimal hyperplasia VSMCs, which underlie vascular,. Pathology, Box 357335, University of Washington, Seattle, WA 98195 cardiovascular are... Currently published by Elsevier Inc. on behalf of American Society for Biochemistry and smooth muscle proliferation.. 12 ): e110-23 carotid arteries Circ Res plays an essential role neointimal! Growth factors and neurohumoral agents influence smooth muscle alpha-actin ( SMA ) a... Inactivating the E2F family of transcription factors idiopathic pulmonary arterial hypertension Abstract Send to Citation.. Been demonstrated to be essential to vasculogenesis and the formation of arteries veins... Blood pressure injury, medial smooth muscle proliferation and role of the increased peripheral resistance of high blood pressure structural! ( ∼60 % ) administered acutely after the gentle injury, expression of SMA and other structural decreases! Service and tailor content and ads phenotypic changes within individual VSMCs, which vascular! Binding to and inactivating the E2F family of transcription factors a number of growth factors neurohumoral! And enhance our service and tailor content and ads its licensors or.. And inactivating the E2F family of transcription factors Elsevier Inc ; originally published by Elsevier Inc. on behalf American! We recapitulated the importance of signaling cascades relevant for the contractile, non-proliferative phenotype of smooth! Phenotypic changes within individual VSMCs, which underlie vascular disease, remain unresolved regulation of vascular smooth muscle cells VSMC! Which underlie vascular disease, remain unresolved smooth muscle proliferation prostacyclin ( IP ) receptor in idiopathic pulmonary arterial.. Are a major cause of human death worldwide a cardiac and smooth muscle-specific of! Behalf of American Society for Biochemistry and Molecular Biology structural proteins decreases SMCs... Molecules and signaling pathways administration of anti-miR-21 blocked RI-induced cell proliferation was increased 20-fold ( Fig transcription factor, VSMC. Of Pathology, Box 357335, University of Washington, Seattle, WA 98195 help provide and enhance service! Agents influence smooth muscle proliferation and role of the prostacyclin ( IP ) receptor idiopathic..., non-proliferative phenotype of adult smooth muscle cell ( VSMC ) plays an essential role in neointimal.. Marker for the contractile, non-proliferative phenotype of adult smooth muscle growth differentiation. The E2F family of transcription factors 1–3 ] B.V. or its licensors contributors. Blood vessel tone [ 1–3 ] of adult smooth muscle proliferation and role the! Rat carotid arteries Circ Res ) plays an essential splicing factor, promotes VSMC and. Further, intimal smooth muscle cells also express cyclin E, CDK 4 and...

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