{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:44:30Z","timestamp":1792075470804,"version":"4.4.0"},"reference-count":110,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>During the development of atherosclerosis and other vascular diseases, vascular smooth muscle cells (SMCs) located in the intima and media of blood vessels shift from a contractile state towards other phenotypes that differ substantially from differentiated SMCs. In addition, these cells acquire new functions, such as the production of alternative extracellular matrix (ECM) proteins and signal molecules. A similar shift in cell phenotype is observed when SMCs are removed from their native environment and placed in a culture, presumably due to the absence of the physiological signals that maintain and regulate the SMC phenotype in the vasculature. The far majority of studies describing SMC functions have been performed under standard culture conditions in which cells adhere to a rigid and static plastic plate. While these studies have contributed to discovering key molecular pathways regulating SMCs, they have a significant limitation: the ECM microenvironment and the mechanical forces transmitted through the matrix to SMCs are generally not considered. Here, we review and discuss the recent literature on how the mechanical forces and derived biochemical signals have been shown to modulate the vascular SMC phenotype and provide new perspectives about their importance.<\/jats:p>","DOI":"10.3390\/cells10092209","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T09:53:23Z","timestamp":1630058003000},"page":"2209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["The Phenotypic Responses of Vascular Smooth Muscle Cells Exposed to Mechanical Cues"],"prefix":"10.3390","volume":"10","author":[{"given":"Lise Filt","family":"Jensen","sequence":"first","affiliation":[{"name":"Atherosclerosis Research Unit, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob Fog","family":"Bentzon","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Unit, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"},{"name":"Experimental Pathology of Atherosclerosis Laboratory, Spanish National Center for Cardiovascular Research (CNIC), 28029 Madrid, Spain"},{"name":"Steno Diabetes Center Aarhus, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2493-1435","authenticated-orcid":false,"given":"Julian","family":"Albarr\u00e1n-Ju\u00e1rez","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Unit, Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJMra1201534","article-title":"Measuring the global burden of disease","volume":"369","author":"Murray","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e721","DOI":"10.1016\/S2214-109X(20)30117-0","article-title":"Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: A systematic review, meta-analysis, and modelling study","volume":"8","author":"Song","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1152\/physrev.1995.75.3.487","article-title":"Regulation of differentiation of vascular smooth muscle cells","volume":"75","author":"Owens","year":"1995","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1161\/CIRCRESAHA.114.302721","article-title":"Mechanisms of plaque formation and rupture","volume":"114","author":"Bentzon","year":"2014","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nrm2596","article-title":"Mechanotransduction in vascular physiology and atherogenesis","volume":"10","author":"Hahn","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1172\/JCI83083","article-title":"Endothelial fluid shear stress sensing in vascular health and disease","volume":"126","author":"Baeyens","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1161\/ATVBAHA.114.303422","article-title":"Shear stress-initiated signaling and its regulation of endothelial function","volume":"34","author":"Zhou","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"861","DOI":"10.3389\/fphys.2020.00861","article-title":"Fluid Shear Stress Sensing by the Endothelial Layer","volume":"11","author":"Roux","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"684","DOI":"10.3389\/fphys.2020.00684","article-title":"The Importance of Mechanical Forces for in vitro Endothelial Cell Biology","volume":"11","author":"Gordon","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/s42003-021-02285-w","article-title":"Integration of substrate- and flow-derived stresses in endothelial cell mechanobiology","volume":"4","author":"Dessalles","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/labinvest.3700215","article-title":"The role of shear stress in the pathogenesis of atherosclerosis","volume":"85","author":"Cunningham","year":"2005","journal-title":"Lab. Invest."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1159\/000339151","article-title":"The effect of pressure-induced mechanical stretch on vascular wall differential gene expression","volume":"49","author":"Anwar","year":"2012","journal-title":"J. Vasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13221-015-0033-z","article-title":"Mechanical stretch: Physiological and pathological implications for human vascular endothelial cells","volume":"7","author":"Jufri","year":"2015","journal-title":"Vascular. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0735-1097(89)90518-4","article-title":"Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: A noninvasive study","volume":"13","author":"Isnard","year":"1989","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1161\/01.HYP.26.1.2","article-title":"Mechanical principles in arterial disease","volume":"26","year":"1995","journal-title":"Hypertension"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13221-015-0032-0","article-title":"Variability in vascular smooth muscle cell stretch-induced responses in 2D culture","volume":"7","author":"Mantella","year":"2015","journal-title":"Vasc. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"0408031","DOI":"10.1115\/1.4043947","article-title":"Regulation of Cell Behavior by Hydrostatic Pressure","volume":"71","author":"Liu","year":"2019","journal-title":"Appl. Mech. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1152\/physrev.00041.2003","article-title":"Molecular regulation of vascular smooth muscle cell differentiation in development and disease","volume":"84","author":"Owens","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1161\/ATVBAHA.119.312131","article-title":"Smooth Muscle Cell Phenotypic Diversity","volume":"39","author":"Liu","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"C59","DOI":"10.1152\/ajpcell.00394.2006","article-title":"Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells","volume":"292","author":"Owens","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00418-015-1386-3","article-title":"An overview of potential molecular mechanisms involved in VSMC phenotypic modulation","volume":"145","author":"Zhang","year":"2016","journal-title":"Histochem. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1016\/j.bbadis.2014.07.008","article-title":"Vascular wall extracellular matrix proteins and vascular diseases","volume":"1842","author":"Xu","year":"2014","journal-title":"Biochim. Biophys. Acta\u2014Mol. Basis Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1016\/j.jacc.2020.03.024","article-title":"Basic Biology of Extracellular Matrix in the Cardiovascular System, Part 1\/4: JACC Focus Seminar","volume":"75","author":"Fischer","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/joim.13034","article-title":"Exploring the role of extracellular matrix proteins to develop biomarkers of plaque vulnerability and outcome","volume":"287","author":"Jonasson","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1016\/j.jacc.2020.03.018","article-title":"Extracellular Matrix in Vascular Disease, Part 2\/4: JACC Focus Seminar","volume":"75","author":"Loeys","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1161\/ATVBAHA.108.178749","article-title":"Molecular mechanisms of collagen isotype-specific modulation of smooth muscle cell phenotype","volume":"29","author":"Orr","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1083\/jcb.107.1.307","article-title":"Diverse effects of fibronectin and laminin on phenotypic properties of cultured arterial smooth muscle cells","volume":"107","author":"Hedin","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1006\/excr.1993.1016","article-title":"Type I collagen promotes modulation of cultured rabbit arterial smooth muscle cells from a contractile to a synthetic phenotype","volume":"204","author":"Yamamoto","year":"1993","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.proeng.2015.07.006","article-title":"Stiffness of Extracellular Matrix Components Modulates the Phenotype of Human Smooth Muscle Cells in Vitro and Allows for the Control of Properties of Engineered Tissues","volume":"110","author":"Timraz","year":"2015","journal-title":"Procedia Engineer."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s40885-018-0102-8","article-title":"Arterial Stiffness and Hypertension","volume":"24","author":"Oh","year":"2018","journal-title":"Clin. Hypertens"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13661","DOI":"10.1073\/pnas.94.25.13661","article-title":"Cell locomotion and focal adhesions are regulated by substrate flexibility","volume":"94","author":"Pelham","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nmeth.3834","article-title":"Measuring cell-generated forces: A guide to the available tools","volume":"13","author":"Polacheck","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.celrep.2012.09.018","article-title":"Cardiovascular protection by ApoE and ApoE-HDL linked to suppression of ECM gene expression and arterial stiffening","volume":"2","author":"Kothapalli","year":"2012","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.biomaterials.2017.11.033","article-title":"Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1","volume":"155","author":"Xie","year":"2018","journal-title":"Biomaterials"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1007\/s12012-020-09580-8","article-title":"Effects of Extracellular Matrix Softening on Vascular Smooth Muscle Cell Dysfunction","volume":"20","author":"Shao","year":"2020","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_36","first-page":"44","article-title":"Substrate Stiffness Affected the Inflammatory Response of SMCs","volume":"9","author":"Mao","year":"2021","journal-title":"J. Biosci. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1021\/acsabm.0c00100","article-title":"Extracellular Matrix Proteins and Substrate Stiffness Synergistically Regulate Vascular Smooth Muscle Cell Migration and Cortical Cytoskeleton Organization","volume":"3","author":"Rickel","year":"2020","journal-title":"Acs. Appl. Bio. Mater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1529\/biophysj.106.089003","article-title":"The stiffness of collagen fibrils influences vascular smooth muscle cell phenotype","volume":"92","author":"McDaniel","year":"2007","journal-title":"Biophys. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1161\/ATVBAHA.117.310237","article-title":"Mining the Stiffness-Sensitive Transcriptome in Human Vascular Smooth Muscle Cells Identifies Long Noncoding RNA Stiffness Regulators","volume":"38","author":"Yu","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.jbiomech.2003.09.011","article-title":"Fibroblast responses to cyclic mechanical stretching depend on cell orientation to the stretching direction","volume":"37","author":"Wang","year":"2004","journal-title":"J. Biomech."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ursekar, C.P., Teo, S.K., Hirata, H., Harada, I., Chiam, K.H., and Sawada, Y. (2014). Design and construction of an equibiaxial cell stretching system that is improved for biochemical analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090665"},{"key":"ref_42","first-page":"518","article-title":"Novel device for application of continuous mechanical tensile strain to mammalian cells","volume":"6","author":"Wada","year":"2017","journal-title":"Biol. Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1002\/bit.25979","article-title":"Unraveling the role of mechanical stimulation on smooth muscle cells: A comparative study between 2D and 3D models","volume":"113","author":"Bono","year":"2016","journal-title":"Biotechnol. Bioeng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1159\/000438544","article-title":"SIRT1 and FOXO Mediate Contractile Differentiation of Vascular Smooth Muscle Cells under Cyclic Stretch","volume":"37","author":"Huang","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.biocel.2014.01.016","article-title":"The role of SIRT6 in the differentiation of vascular smooth muscle cells in response to cyclic strain","volume":"49","author":"Yao","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/cvr\/cvs274","article-title":"Cyclic stretch-induced thrombin generation by rat vascular smooth muscle cells is mediated by the integrin \u03b1v\u03b23 pathway","volume":"96","author":"Mao","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1161\/ATVBAHA.114.304936","article-title":"MEF2B-Nox1 signaling is critical for stretch-induced phenotypic modulation of vascular smooth muscle cells","volume":"35","author":"Ranayhossaini","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/cvr\/cvs247","article-title":"Hypertension impairs myocardin function: A novel mechanism facilitating arterial remodelling","volume":"96","author":"Pfisterer","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1159\/000495376","article-title":"Arterial Wall Stress Induces Phenotypic Switching of Arterial Smooth Muscle Cells in Vascular Remodeling by Activating the YAP\/TAZ Signaling Pathway","volume":"51","author":"Wang","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.biocel.2014.11.011","article-title":"Involvement of BK channel in differentiation of vascular smooth muscle cells induced by mechanical stretch","volume":"59","author":"Wan","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hu, B., Song, J.T., Qu, H.Y., Bi, C.L., Huang, X.Z., Liu, X.X., and Zhang, M. (2014). Mechanical stretch suppresses microRNA-145 expression by activating extracellular signal-regulated kinase 1\/2 and upregulating angiotensin- converting enzyme to alter vascular smooth muscle cell phenotype. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096338"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s11010-017-3065-2","article-title":"Fingerprint of long non-coding RNA regulated by cyclic mechanical stretch in human aortic smooth muscle cells: Implications for hypertension","volume":"435","author":"Mantella","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1006\/exmp.2000.2321","article-title":"Effects of extracellular matrix on phenotype modulation and MAPK transduction of rat aortic smooth muscle cells in vitro","volume":"69","author":"Qin","year":"2000","journal-title":"Exp. Mol. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1423-0127-20-50","article-title":"Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells","volume":"20","author":"Chiu","year":"2013","journal-title":"J. Biomed. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1039\/c3lc50894c","article-title":"A novel system for studying mechanical strain waveform-dependent responses in vascular smooth muscle cells","volume":"13","author":"Lee","year":"2013","journal-title":"Lab. Chip"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"H2946","DOI":"10.1152\/ajpheart.00919.2004","article-title":"Biomechanical stress induces IL-6 expression in smooth muscle cells via Ras\/Rac1-p38 MAPK-NF-kappaB signaling pathways","volume":"288","author":"Zampetaki","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16128","DOI":"10.1038\/s41598-017-15867-8","article-title":"Chemokines protect vascular smooth muscle cells from cell death induced by cyclic mechanical stretch","volume":"7","author":"Zhao","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"BSR20192012","DOI":"10.1042\/BSR20192012","article-title":"Physiological cyclic stretch up-regulates angiotensin-converting enzyme 2 expression to reduce proliferation and migration of vascular smooth muscle cells","volume":"40","author":"Song","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1002\/jcb.22465","article-title":"Cyclic strain modulates migration and proliferation of vascular smooth muscle cells via Rho-GDI\u03b1, Rac1, and p38 pathway","volume":"109","author":"Qi","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_60","first-page":"2106","article-title":"Mechanical stress-activated PKCdelta regulates smooth muscle cell migration","volume":"17","author":"Li","year":"2003","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"H748","DOI":"10.1152\/ajpheart.2000.278.3.H748","article-title":"Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells","volume":"278","author":"Chapman","year":"2000","journal-title":"Am. J. Physiol. \u2014Heart Circ. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/2045-824X-3-21","article-title":"Cyclic strain upregulates VEGF and attenuates proliferation of vascular smooth muscle cells","volume":"3","author":"Schad","year":"2011","journal-title":"Vascular. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ping, S., Li, Y., Liu, S., Zhang, Z., Wang, J., Zhou, Y., Liu, K., Huang, J., Chen, D., and Wang, J. (2015). Simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells accelerate diabetic mouse venous atherosclerosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141375"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/s10753-017-0653-y","article-title":"Biomechanical Stretch Induces Inflammation, Proliferation, and Migration by Activating NFAT5 in Arterial Smooth Muscle Cells","volume":"40","author":"Cao","year":"2017","journal-title":"Inflammation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"540591","DOI":"10.3389\/fphys.2020.540591","article-title":"Mechanical Stretch Induces Smooth Muscle Cell Dysfunction by Regulating ACE2 via P38\/ATF3 and Post-transcriptional Regulation by miR-421","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Song, J.t., Hu, B., Qu, H.y., Bi, C.l., Huang, X.z., and Zhang, M. (2012). Mechanical Stretch Modulates MicroRNA 21 Expression, Participating in Proliferation and Apoptosis in Cultured Human Aortic Smooth Muscle Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047657"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.7150\/ijbs.56247","article-title":"Dickkopf-1 promotes Vascular Smooth Muscle Cell proliferation and migration through upregulating UHRF1 during Cyclic Stretch application","volume":"17","author":"Zheng","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41569-019-0227-9","article-title":"Vascular smooth muscle cells in atherosclerosis","volume":"16","author":"Basatemur","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1161\/ATVBAHA.111.235622","article-title":"Smooth muscle cell apoptosis promotes vessel remodeling and repair via activation of cell migration, proliferation, and collagen synthesis","volume":"31","author":"Yu","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/S0531-5565(01)00090-0","article-title":"Smooth muscle cell apoptosis in arteriosclerosis","volume":"36","author":"Mayr","year":"2001","journal-title":"Exp. Gerontol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00059-016-4489-2","article-title":"Role of nifedipine and hydrochlorothiazide in MAPK activation and vascular smooth muscle cell proliferation and apoptosis","volume":"42","author":"Wang","year":"2017","journal-title":"Herz"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"118253","DOI":"10.1016\/j.lfs.2020.118253","article-title":"Berberine inhibits proliferation and apoptosis of vascular smooth muscle cells induced by mechanical stretch via the PDI\/ERS and MAPK pathways","volume":"259","author":"Wang","year":"2020","journal-title":"Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2818","DOI":"10.1038\/cddis.2017.213","article-title":"Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis","volume":"8","author":"Ping","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zhao, J., Ozawa, K., Kyotani, Y., Nagayama, K., Ito, S., Komatsubara, A.T., Tsuji, Y., and Yoshizumi, M. (2014). Azelnidipine inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102813"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zhao, J., Nakahira, K., Kimura, A., Kyotani, Y., and Yoshizumi, M. (2020). Upregulation of iNOS Protects Cyclic Mechanical Stretch-Induced Cell Death in Rat Aorta Smooth Muscle Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228660"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1093\/cvr\/cvr280","article-title":"Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells","volume":"93","author":"Cheng","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/path.4534","article-title":"Mechanical stretch-induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection","volume":"236","author":"Jia","year":"2015","journal-title":"J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1115\/1.2794192","article-title":"Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells","volume":"117","author":"Wang","year":"1995","journal-title":"J. Biomech. Eng."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"H1196","DOI":"10.1152\/ajpheart.00499.2009","article-title":"Enhanced interstitial flow as a contributing factor in neointima formation: (shear) stressing vascular wall cell types other than the endothelium","volume":"297","author":"Rizzo","year":"2009","journal-title":"Am. J. Physiol.-Heart C"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Shi, Z.D., Abraham, G., and Tarbell, J.M. (2010). Shear stress modulation of smooth muscle cell marker genes in 2-D and 3-D depends on mechanotransduction by heparan sulfate proteoglycans and ERK1\/2. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012196"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s12195-011-0205-8","article-title":"Effects of Fluid Shear Stress on a Distinct Population of Vascular Smooth Muscle Cells","volume":"4","author":"Hsu","year":"2011","journal-title":"Cell Mol. Bioeng."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1161\/ATVBAHA.116.307893","article-title":"Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM","volume":"36","author":"Rykaczewska","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s10571-017-0505-1","article-title":"Shear Stress Induces Phenotypic Modulation of Vascular Smooth Muscle Cells via AMPK\/mTOR\/ULK1-Mediated Autophagy","volume":"38","author":"Sun","year":"2018","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jvs.2010.02.282","article-title":"Tissue factor pathway inhibitor-2 is induced by fluid shear stress in vascular smooth muscle cells and affects cell proliferation and survival","volume":"52","author":"Ekstrand","year":"2010","journal-title":"J. Vasc. Surg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"H76","DOI":"10.1152\/ajpheart.00905.2010","article-title":"Vascular smooth muscle cell glycocalyx modulates shear-induced proliferation, migration, and NO production responses","volume":"300","author":"Kang","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/jcp.21404","article-title":"Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway","volume":"216","author":"Fitzgerald","year":"2008","journal-title":"J. Cell Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1084\/jem.20180483","article-title":"Piezo1 and Gq\/G11 promote endothelial inflammation depending on flow pattern and integrin activation","volume":"215","author":"Iring","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S0741-5214(03)00329-X","article-title":"Oscillatory shear stress increases smooth muscle cell proliferation and Akt phosphorylation","volume":"37","author":"Haga","year":"2003","journal-title":"J. Vasc. Surg."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"824","DOI":"10.3389\/fphys.2018.00824","article-title":"Cellular Mechanotransduction: From Tension to Function","volume":"9","author":"Martino","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1365-2796.2006.01624.x","article-title":"Molecular mechanisms of the vascular responses to haemodynamic forces","volume":"259","author":"Lehoux","year":"2006","journal-title":"J. Intern. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1210\/en.2002-220939","article-title":"Activation of cell adhesion kinase beta by mechanical stretch in vascular smooth muscle cells","volume":"144","author":"Iwasaki","year":"2003","journal-title":"Endocrinology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e001712","DOI":"10.1161\/JAHA.114.001712","article-title":"Loss of the mechanotransducer zyxin promotes a synthetic phenotype of vascular smooth muscle cells","volume":"4","author":"Ghosh","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"28","DOI":"10.2174\/1874120700903010028","article-title":"Effects of cyclic strain and growth factors on vascular smooth muscle cell responses","volume":"3","author":"Kona","year":"2009","journal-title":"Open Biomed. Eng. J."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1161\/01.RES.0000159182.98874.43","article-title":"Cyclic strain inhibits Notch receptor signaling in vascular smooth muscle cells in vitro","volume":"96","author":"Morrow","year":"2005","journal-title":"Circ. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/ncb1137","article-title":"Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II","volume":"6","author":"Zou","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"C456","DOI":"10.1152\/ajpcell.00057.2002","article-title":"Stretch-induced Ca(2+) release via an IP(3)-insensitive Ca(2+) channel","volume":"283","author":"Mohanty","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.lfs.2008.04.013","article-title":"Cyclic stretch decreases TRPC4 protein and capacitative calcium entry in rat vascular smooth muscle cells","volume":"83","author":"Lindsey","year":"2008","journal-title":"Life Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-3-030-63164-2_9","article-title":"Mechanical Regulation of Epigenetic Modifications in Vascular Biology and Pathobiology","volume":"Volume 8","author":"Duncker","year":"2021","journal-title":"Vascular Mechanobiology in Physiology and Disease. Cardiac and Vascular Biology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12079-020-00576-1","article-title":"Biomechanical signal communication in vascular smooth muscle cells","volume":"14","author":"Chen","year":"2020","journal-title":"J. Cell Commun. Signal."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.jbiomech.2009.01.012","article-title":"Histone deacetylases modulate vascular smooth muscle cell migration induced by cyclic mechanical strain","volume":"42","author":"Yan","year":"2009","journal-title":"J. Biomech."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.carpath.2007.03.001","article-title":"The effects of stretch on vascular smooth muscle cell phenotype in vitro","volume":"17","author":"Halka","year":"2008","journal-title":"Cardiovasc. Pathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1161\/01.RES.85.1.5","article-title":"Mechanotransduction of rat aortic vascular smooth muscle cells requires RhoA and intact actin filaments","volume":"85","author":"Numaguchi","year":"1999","journal-title":"Circ. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1093\/eurheartj\/ehab068","article-title":"A call to action for new global approaches to cardiovascular disease drug solutions","volume":"42","author":"Figtree","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1152\/japplphysiol.01114.2004","article-title":"Mechanical, biochemical, and extracellular matrix effects on vascular smooth muscle cell phenotype","volume":"98","author":"Stegemann","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/1535370219892574","article-title":"Effects of Caveolin-1-ERK1\/2 pathway on endothelial cells and smooth muscle cells under shear stress","volume":"245","author":"Jia","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e1900249","DOI":"10.1002\/adbi.201900249","article-title":"Human In Vitro Model Mimicking Material-Driven Vascular Regeneration Reveals How Cyclic Stretch and Shear Stress Differentially Modulate Inflammation and Matrix Deposition","volume":"4","author":"Wissing","year":"2020","journal-title":"Adv. Biosyst."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1038\/s41467-018-06891-x","article-title":"Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels","volume":"9","author":"Dobnikar","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1161\/CIRCULATIONAHA.120.048378","article-title":"Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human","volume":"142","author":"Pan","year":"2020","journal-title":"Circulation"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s41591-019-0512-5","article-title":"Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis","volume":"25","author":"Wirka","year":"2019","journal-title":"Nat. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.tcb.2021.02.008","article-title":"Mechanical Regulation of Transcription: Recent Advances","volume":"31","author":"Wagh","year":"2021","journal-title":"Trends Cell Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/9\/2209\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:52:59Z","timestamp":1760165579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/9\/2209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,26]]},"references-count":110,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cells10092209"],"URL":"https:\/\/doi.org\/10.3390\/cells10092209","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,26]]}}}