{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:57:10Z","timestamp":1789102630020,"version":"build-2803163510"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/00509-1"],"award-info":[{"award-number":["2017\/00509-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Arterial stiffness, frequently associated with hypertension, is associated with disorganization of the vascular wall and has been recognized as an independent predictor of all-cause mortality. The identification of the molecular mechanisms involved in aortic stiffness would be an emerging target for hypertension therapeutic intervention. This study evaluated the effects of perindopril on pulse wave velocity (PWV) and on the differentially expressed proteins in aorta of spontaneously hypertensive rats (SHR), using a proteomic approach. SHR and Wistar rats were treated with perindopril (SHR<jats:sub>P<\/jats:sub>) or water (SHRc and Wistar rats) for 8 weeks. At the end, SHR<jats:sub>C<\/jats:sub> presented higher systolic blood pressure (SBP, +70%) and PWV (+31%) compared with Wistar rats. SHR<jats:sub>P<\/jats:sub> had higher values of nitrite concentration and lower PWV compared with SHR<jats:sub>C<\/jats:sub>. From 21 upregulated proteins in the aortic wall from SHR<jats:sub>C<\/jats:sub>, most of them were involved with the actin cytoskeleton organization, like <jats:italic>Tropomyosin<\/jats:italic> and <jats:italic>Cofilin-1<\/jats:italic>. After perindopril treatment, there was an upregulation of the <jats:italic>GDP dissociation inhibitors<\/jats:italic> (<jats:italic>GDIs<\/jats:italic>), which normally inhibits the <jats:italic>RhoA\/Rho-kinase\/cofilin-1<\/jats:italic> pathway and may contribute to decreased arterial stiffening. In conclusion, the results of the present study revealed that treatment with perindopril reduced SBP and PWV in SHR. In addition, the proteomic analysis in aorta suggested, for the first time, that the <jats:italic>RhoA\/Rho-kinase\/Cofilin-1<\/jats:italic> pathway may be inhibited by perindopril-induced upregulation of <jats:italic>GDIs<\/jats:italic> or increases in NO bioavailability in SHR. Therefore, we may propose that activation of <jats:italic>GDIs<\/jats:italic> or inhibition of <jats:italic>RhoA\/Rho-kinase<\/jats:italic> pathway could be a possible strategy to treat arterial stiffness.<\/jats:p>","DOI":"10.3389\/fphys.2021.624515","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T15:32:43Z","timestamp":1612971163000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of Aortic Proteins Involved in Arterial Stiffness in Spontaneously Hypertensive Rats Treated With Perindopril:A Proteomic Approach"],"prefix":"10.3389","volume":"12","author":[{"given":"Danyelle S.","family":"Miotto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Dionizio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 M.","family":"Jacomini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson S.","family":"Zago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00edlia Afonso Rabelo","family":"Buzalaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Amaral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1097\/00004872-200018110-00006","article-title":"Exercise training normalizes wall-to-lumen ratio of the gracilis muscle arterioles and reduces pressure in spontaneously hypertensive rats.","volume":"18","author":"Amaral","year":"2000","journal-title":"J. Hypertens."},{"key":"B2","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1161\/hypertensionaha.109.142190","article-title":"Arterial stiffness is regulated by nitric oxide and endothelium-derived hyperpolarizing factor during changes in blood flow in humans.","volume":"55","author":"Bellien","year":"2010","journal-title":"Hypertension"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.1089\/ars.2013.5566","article-title":"Tetrahydrobiopterin in cardiovascular health and disease.","volume":"20","author":"Bendall","year":"2014","journal-title":"Antioxidants Redox Signal."},{"key":"B4","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ejcb.2007.09.001","article-title":"A proteomic analysis of aorta from spontaneously hypertensive rat: RhoGDI alpha upregulation by angiotensin II via AT(1) receptor.","volume":"87","author":"Bian","year":"2008","journal-title":"Eur. J. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1093\/bioinformatics\/btt019","article-title":"CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data.","volume":"29","author":"Bindea","year":"2013","journal-title":"Bioinformatics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1124\/pr.115.010652","article-title":"Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders.","volume":"68","author":"Brozovich","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1161\/01.hyp.23.4.439","article-title":"Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides.","volume":"23","author":"Campbell","year":"1994","journal-title":"Hypertension"},{"key":"B9","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.cardiores.2006.10.021","article-title":"ACE inhibition with perindopril and endothelial function. results of a substudy of the EUROPA study: PERTINENT.","volume":"73","author":"Ceconi","year":"2007","journal-title":"Cardiovas. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1111\/1756-185x.12689","article-title":"Central arterial characteristics of gout patients with chronic kidney diseases.","volume":"20","author":"Celik","year":"2017","journal-title":"Int. J. Rheumatic Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1097\/01.mbp.0000209084.55364.3a","article-title":"Impaired aortic elastic properties in young patients with prehypertension.","volume":"11","author":"Celik","year":"2006","journal-title":"Blood Press. Monitor."},{"key":"B12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.mcna.2016.08.016","article-title":"Guidelines for the management of hypertension.","volume":"101","author":"Chobanian","year":"2017","journal-title":"Med. Clin. North Am."},{"key":"B13","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.phrs.2017.10.003","article-title":"Treatment of hypertension: the ESH\/ESC guidelines recommendations.","volume":"128","author":"Cuspidi","year":"2018","journal-title":"Pharmacol. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1080\/14789450.2018.1493927","article-title":"Utilizing proteomics to understand and define hypertension: where are we and where do we go?","volume":"15","author":"Delles","year":"2018","journal-title":"Exp. Rev. Proteom."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.140419","article-title":"Effects of acute fluoride exposure on the jejunum and ileum of rats: insights from proteomic and enteric innervation analysis.","volume":"741","author":"Dionizio","year":"2020","journal-title":"Sci. Total Environ."},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-21533-4","article-title":"Chronic treatment with fluoride affects the jejunum: insights from proteomics and enteric innervation analysis.","volume":"8","author":"Dionizio","year":"2018","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.jash.2018.06.004","article-title":"Short-term exposure to dexamethasone promotes autonomic imbalance to the heart before hypertension.","volume":"12","author":"Duchatsch","year":"2018","journal-title":"J. Am. Soc. Hypertension : JASH."},{"key":"B18","doi-asserted-by":"publisher","first-page":"572","DOI":"10.2340\/16501977-1148","article-title":"Short-term cardiovascular physical programme ameliorates arterial stiffness and decreases oxidative stress in women with metabolic syndrome.","volume":"45","author":"Eleuterio-Silva","year":"2013","journal-title":"J. Rehabil. Med."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.mex.2020.100901","article-title":"Standardization of a new non-invasive device for assessment of arterial stiffness in rats: correlation with age-related arteries\u2019 structure.","volume":"7","author":"Fabricio","year":"2020","journal-title":"MethodsX."},{"key":"B20","doi-asserted-by":"publisher","first-page":"681","DOI":"10.3892\/br.2015.488","article-title":"Aortic wall proteomic analysis in spontaneously hypertensive rats with a blood pressure decrease induced by 6-week load-free swimming.","volume":"3","author":"Feng","year":"2015","journal-title":"Biomed. Rep."},{"key":"B21","doi-asserted-by":"crossref","first-page":"142S","DOI":"10.1016\/j.amjhyper.2005.05.037","article-title":"Specific properties and effect of perindopril in controlling the renin-angiotensin system.","volume":"18","author":"Ferrari","year":"2005","journal-title":"Am. J. Hypertension"},{"key":"B22","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1161\/HYPERTENSIONAHA.118.11125","article-title":"Myocardial remodeling in hypertension.","volume":"72","author":"Gonzalez","year":"2018","journal-title":"Hypertension"},{"key":"B23","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.ejmech.2013.10.048","article-title":"Advances in the studies of roles of Rho\/Rho-kinase in diseases and the development of its inhibitors.","volume":"70","author":"Guan","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1042\/cs20070080","article-title":"Arterial stiffness: clinical relevance, measurement and treatment.","volume":"113","author":"Hamilton","year":"2007","journal-title":"Clin. Sci. (Lond)."},{"key":"B25","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/ajh.2008.199","article-title":"Regulation of myosin light chain kinase expression by angiotensin II in hypertension.","volume":"21","author":"Han","year":"2008","journal-title":"Am. J. Hypertension"},{"key":"B26","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s11845-013-0963-5","article-title":"The effects of angiotensin-converting enzyme-inhibitory peptide LAP on the left common carotid artery remodeling in spontaneously hypertensive rats.","volume":"182","author":"Hong","year":"2013","journal-title":"Irish J. Med. Sci."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00122","article-title":"Influence of estimated training status on anti and pro-oxidant activity, nitrite concentration, and blood pressure in middle-aged and older women.","volume":"8","author":"Jacomini","year":"2017","journal-title":"Front. Physiol."},{"key":"B28","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/621437","article-title":"Arterial stiffness and cardiovascular therapy.","volume":"2014","author":"Janic","year":"2014","journal-title":"BioMed Res. Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1001\/2012.jama.10503","article-title":"Aortic stiffness, blood pressure progression, and incident hypertension.","volume":"308","author":"Kaess","year":"2012","journal-title":"JAMA"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/bf03324634","article-title":"Production of nitric oxide, lipid peroxidation and oxidase activity of ceruloplasmin in blood of elderly patients with primary hypertension. effects of perindopril treatment.","volume":"18","author":"Kedziora-Kornatowska","year":"2006","journal-title":"Aging Clin. Exp. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.1097\/01.asn.0000094085.04161.a7","article-title":"Nitric oxide inhibits stretch-induced MAPK activation in mesangial cells through RhoA inactivation.","volume":"14","author":"Krepinsky","year":"2003","journal-title":"J. Am. Soc. Nephrol. JASN."},{"key":"B32","first-page":"168","article-title":"Role of MMP-2 and MMP-9 in resistance to drug therapy in patients with resistant hypertension.","volume":"105","author":"Lacerda","year":"2015","journal-title":"Arquivos Brasileiros de Cardiologia."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1152\/physrev.00003.2017","article-title":"Vascular smooth muscle cells and arterial stiffening: relevance in development.","volume":"97","author":"Lacolley","year":"2017","journal-title":"Aging Dis. Physiol. Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1182\/blood-2006-08-043570","article-title":"Chemotherapy exposure increases leukemia cell stiffness.","volume":"109","author":"Lam","year":"2007","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1172\/jci200314172","article-title":"Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension.","volume":"111","author":"Landmesser","year":"2003","journal-title":"J. Clin. Invest."},{"key":"B36","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1161\/hypertensionaha.109.133116","article-title":"Large and small artery cross-talk and recent morbidity-mortality trials in hypertension.","volume":"54","author":"Laurent","year":"2009","journal-title":"Hypertension"},{"key":"B37","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1002\/pmic.200800973","article-title":"Diminished expression of dihydropteridine reductase is a potent biomarker for hypertensive vessels.","volume":"9","author":"Lee","year":"2009","journal-title":"Proteomics"},{"key":"B38","doi-asserted-by":"publisher","first-page":"6455","DOI":"10.1002\/pmic.200600124","article-title":"Proteomic profiling and identification of cofilin responding to oxidative stress in vascular smooth muscle.","volume":"6","author":"Lee","year":"2006","journal-title":"Proteomics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1161\/01.hyp.0000148303.98066.ab","article-title":"Hypertension and RhoA\/Rho-kinase signaling in the vasculature: highlights from the recent literature.","volume":"44","author":"Lee","year":"2004","journal-title":"Hypertension"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106646","article-title":"Proteomic analysis of gastrocnemius muscle in rats with streptozotocin-induced diabetes and chronically exposed to fluoride.","volume":"9","author":"Lima Leite","year":"2014","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1159\/000488877","article-title":"Differential stiffening between the abdominal and thoracic aorta: effect of salt loading in stroke-prone hypertensive rats.","volume":"55","author":"Lindesay","year":"2018","journal-title":"J. Vascular Res."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12805","article-title":"Age and hypertension strongly induce aortic stiffening in rats at basal and matched blood pressure levels.","volume":"4","author":"Lindesay","year":"2016","journal-title":"Physiol. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/j.1440-1681.1992.tb02811.x","article-title":"Comparison of the pharmacokinetics and pharmacodynamics of perindopril, cilazapril and enalapril.","volume":"19","author":"Louis","year":"1992","journal-title":"Clin. Exp. Pharmacol. Physiol. Suppl."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1161\/atvbaha.114.304706","article-title":"Proteome analysis of human arterial tissue discloses associations between the vascular content of small leucine-rich repeat proteoglycans and pulse wave velocity.","volume":"35","author":"Lyck Hansen","year":"2015","journal-title":"Arteriosclerosis Thrombosis Vasc. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/s0895-7061(01)02313-5","article-title":"Reduction in arterial stiffness with angiotensin II antagonist is comparable with and additive to ACE inhibition.","volume":"15","author":"Mahmud","year":"2002","journal-title":"Am. J. Hypertension."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12298","article-title":"Effect of different drug classes on reverse remodeling of intramural coronary arterioles in the spontaneously hypertensive rat.","volume":"24","author":"Mancini","year":"2017","journal-title":"Microcirculation"},{"key":"B47","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1046\/j.1440-1681.2002.03747.x","article-title":"Withdrawal reveals lack of effect of prolonged antihypertensive treatment on intrinsic aortic wall stiffness in senescent spontaneously hypertensive rats.","volume":"29","author":"Marque","year":"2002","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1161\/hy1201.096541","article-title":"Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans.","volume":"38","author":"Masumoto","year":"2001","journal-title":"Hypertension"},{"key":"B49","doi-asserted-by":"publisher","first-page":"8467","DOI":"10.1128\/mcb.22.24.8467-8477.2002","article-title":"Rho GTPase\/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B\/Akt in human endothelial cells.","volume":"22","author":"Ming","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1161\/hypertensionaha.114.00921","article-title":"Arterial stiffness and hypertension.","volume":"64","author":"Mitchell","year":"2014","journal-title":"Hypertension"},{"key":"B51","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1161\/circulationaha.109.886655","article-title":"Arterial stiffness and cardiovascular events: the framingham heart study.","volume":"121","author":"Mitchell","year":"2010","journal-title":"Circulation"},{"key":"B52","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1161\/hypertensionaha.120.15203","article-title":"LIMK (LIM Kinase) inhibition prevents vasoconstriction- and hypertension-induced arterial stiffening and remodeling.","volume":"76","author":"Morales-Quinones","year":"2020","journal-title":"Hypertension"},{"key":"B53","doi-asserted-by":"crossref","DOI":"10.1186\/1476-7120-12-37","article-title":"In vivo assessment of arterial stiffness in the isoflurane anesthetized spontaneously hypertensive rat.","volume":"12","author":"Morgan","year":"2014","journal-title":"Cardiovasc. Ultrasound"},{"key":"B54","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1291\/hypres.27.263","article-title":"RhoA activation in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats.","volume":"27","author":"Moriki","year":"2004","journal-title":"Hypertension Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1291\/hypres.28.937","article-title":"Selective angiotensin receptor antagonism with valsartan decreases arterial stiffness independently of blood pressure lowering in hypertensive patients.","volume":"28","author":"Nakamura","year":"2005","journal-title":"Hypertension Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.carpath.2015.11.003","article-title":"Resveratrol improves vasoprotective effects of captopril on aortic remodeling and fibrosis triggered by renovascular hypertension.","volume":"25","author":"Natalin","year":"2016","journal-title":"Cardiovasc. Pathol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1161\/hypertensionaha.116.08917","article-title":"Aortic-Brachial arterial stiffness gradient and cardiovascular risk in the community: the framingham heart study.","volume":"69","author":"Niiranen","year":"2017","journal-title":"Hypertension"},{"key":"B58","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1177\/0003319719857270","article-title":"A vascular aging index as independent predictor of cardiovascular events and total mortality in an elderly urban population.","volume":"70","author":"Nilsson Wadstrom","year":"2019","journal-title":"Angiology"},{"key":"B59","doi-asserted-by":"crossref","DOI":"10.1080\/21541248.2020.1822721","article-title":"New insights into RhoA\/Rho-kinase signaling: a key regulator of vascular contraction.","author":"Nunes","year":"2020","journal-title":"Small GTPases"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1097\/hjh.0000000000001371","article-title":"Evaluation of arterial stiffness by finger-toe pulse wave velocity: optimization of signal processing and clinical validation.","volume":"35","author":"Obeid","year":"","journal-title":"J. Hypertension"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1088\/1361-6579\/aa905a","article-title":"Numerical assessment and comparison of pulse wave velocity methods aiming at measuring aortic stiffness.","volume":"38","author":"Obeid","year":"","journal-title":"Physiol. Measurement"},{"key":"B62","article-title":"Association of aortic stiffness with left ventricular remodeling and reduced left ventricular function measured by magnetic resonance imaging: the multi-ethnic study of atherosclerosis.","volume":"9","author":"Ohyama","year":"2016","journal-title":"Circul. Cardiovascular Imag."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1097\/hjh.0b013e328346a583","article-title":"Aortic stiffness is reduced beyond blood pressure lowering by short-term and long-term antihypertensive treatment: a meta-analysis of individual data in 294 patients.","volume":"29","author":"Ong","year":"2011","journal-title":"J. Hypertension"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107527","article-title":"Evaluating the benefits of renin-angiotensin system inhibitors as cancer treatments.","volume":"211","author":"Perini","year":"2020","journal-title":"Pharmacol. Therapeut."},{"key":"B65","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1139\/apnm-2014-0206","article-title":"The association between arterial properties and blood pressure in children.","volume":"40","author":"Phillips","year":"2015","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237237","article-title":"Genome-wide association analysis of pulse wave velocity traits provide new insights into the causal relationship between arterial stiffness and blood pressure.","volume":"15","author":"Rode","year":"2020","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1111\/j.1476-5381.2012.02224.x","article-title":"Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension.","volume":"168","author":"Roque","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"167","DOI":"10.2147\/ijnrd.s6664","article-title":"Effect of angiotensin II blockade on central blood pressure and arterial stiffness in subjects with hypertension.","volume":"3","author":"Safar","year":"2010","journal-title":"Int. J. Nephrol. Renovascular Dis."},{"key":"B69","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.ijcard.2009.04.027","article-title":"Arterial stiffness: methods of measurement, physiologic determinants and prediction of cardiovascular outcomes.","volume":"138","author":"Sakuragi","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"9472","DOI":"10.1074\/jbc.m212776200","article-title":"RhoA expression is controlled by nitric oxide through cGMP-dependent protein kinase activation.","volume":"278","author":"Sauzeau","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/s0167-0115(00)00178-6","article-title":"The multiple actions of angiotensin II in atherosclerosis.","volume":"93","author":"Schmidt-Ott","year":"2000","journal-title":"Regulat. Peptides"},{"key":"B72","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s40520-019-01260-0","article-title":"Arterial stiffness and multiple organ damage: a longitudinal study in population.","volume":"32","author":"Scuteri","year":"2020","journal-title":"Aging Clin. Exp. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1161\/01.res.0000059987.90200.44","article-title":"Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle.","volume":"92","author":"Seko","year":"2003","journal-title":"Circulat. Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.bbamcr.2018.10.003","article-title":"Cofilin-1 signaling mediates epithelial-mesenchymal transition by promoting actin cytoskeleton reorganization and cell-cell adhesion regulation in colorectal cancer cells.","volume":"1866","author":"Sousa-Squiavinato","year":"2019","journal-title":"Biochimica et Biophysica acta Mol. Cell Res."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00824","article-title":"Restoring blood pressure in hypertensive mice fails to fully reverse vascular stiffness.","volume":"11","author":"Steppan","year":"2020","journal-title":"Front. Physiol."},{"key":"B76","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/cvr\/cvy023","article-title":"Vascular smooth muscle contraction in hypertension.","volume":"114","author":"Touyz","year":"2018","journal-title":"Cardiovascular Res."},{"key":"B77","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1007\/s11255-014-0753-7","article-title":"Associations between serum hepcidin level, FGF-21 level and oxidative stress with arterial stiffness in CAPD patients.","volume":"46","author":"Ulu","year":"2014","journal-title":"Int. Urol. Nephrol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1161\/hypertensionaha.120.15026","article-title":"International society of hypertension global hypertension practice guidelines.","volume":"75","author":"Unger","year":"2020","journal-title":"Hypertension"},{"key":"B79","doi-asserted-by":"crossref","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"UniProt: a worldwide hub of protein knowledge.","volume":"47","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B80","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1159\/000321471","article-title":"Salt-induced renal injury in spontaneously hypertensive rats: effects of nebivolol.","volume":"32","author":"Varagic","year":"2010","journal-title":"Am. J. Nephrol."},{"key":"B81","doi-asserted-by":"crossref","first-page":"H382","DOI":"10.1152\/ajpheart.00094.2011","article-title":"Aortic stiffness in vivo in hypertensive rat via echo-tracking: analysis of the pulsatile distension waveform.","volume":"301","author":"Vayssettes-Courchay","year":"2011","journal-title":"Am. J. Physiol. Heart Circulatory Physiol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1016\/j.jacc.2009.10.061","article-title":"Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis.","volume":"55","author":"Vlachopoulos","year":"2010","journal-title":"J. Am. College Cardiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s12265-012-9349-8","article-title":"Elastin in large artery stiffness and hypertension.","volume":"5","author":"Wagenseil","year":"2012","journal-title":"J. Cardiovascular Transl. Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1002\/iub.527","article-title":"Vascular smooth muscle myosin light chain diphosphorylation: mechanism, function, and pathological implications.","volume":"63","author":"Walsh","year":"2011","journal-title":"IUBMB Life"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1124\/jpet.103.062265","article-title":"Rho\/Rho kinase and phosphoinositide 3-kinase are parallel pathways in the development of spontaneous arterial tone in deoxycorticosterone acetate-salt hypertension.","volume":"309","author":"Wehrwein","year":"2004","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"B86","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41374-018-0116-6","article-title":"The cofilin phosphatase slingshot homolog 1 restrains angiotensin II-induced vascular hypertrophy and fibrosis in vivo.","volume":"99","author":"Williams","year":"2019","journal-title":"Lab. Invest. J. Techn. Methods Pathol."},{"key":"B87","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/615312","article-title":"The role of oxidative stress and inflammation in cardiovascular aging.","volume":"2014","author":"Wu","year":"2014","journal-title":"BioMed Res. Int."},{"key":"B88","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jash.2008.09.002","article-title":"Vascular smooth muscle cell signaling mechanisms for contraction to angiotensin II and endothelin-1.","volume":"3","author":"Wynne","year":"2009","journal-title":"J. Am. Soc. Hypertension : JASH."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.cardfail.2011.09.002","article-title":"Angiotensin-converting enzyme inhibition promotes coronary angiogenesis in the failing heart of dahl salt-sensitive hypertensive rats.","volume":"17","author":"Yazawa","year":"2011","journal-title":"J. Cardiac Failure"},{"key":"B90","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.amjhyper.2004.05.006","article-title":"Increaseed expression of mRNA for regulator of G protein signaling domain-containing Rho guanine nucleotide exchange factors in aorta from stroke-prone spontaneously hypertensive rats.","volume":"17","author":"Ying","year":"2004","journal-title":"Am. J. Hypertension"},{"key":"B91","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1159\/000485284","article-title":"Rho kinase regulates aortic vascular smooth muscle cell stiffness Via Actin\/SRF\/Myocardin in hypertension.","volume":"44","author":"Zhou","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"B92","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1161\/01.atv.0000160548.78317.29","article-title":"Mechanisms, pathophysiology, and therapy of arterial stiffness.","volume":"25","author":"Zieman","year":"2005","journal-title":"Arteriosclerosis Thrombosis Vascular Biol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.624515\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T15:32:58Z","timestamp":1612971178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.624515\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,10]]},"references-count":92,"alternative-id":["10.3389\/fphys.2021.624515"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.624515","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,10]]},"article-number":"624515"}}