Integrins, Vascular Remodeling, and Hypertension
2006; Lippincott Williams & Wilkins; Volume: 49; Issue: 1 Linguagem: Inglês
10.1161/01.hyp.0000252753.63224.3b
ISSN1524-4563
AutoresEgidius H.J. Heerkens, Ashley S. Izzard, Anthony M. Heagerty,
Tópico(s)Angiogenesis and VEGF in Cancer
ResumoHomeHypertensionVol. 49, No. 1Integrins, Vascular Remodeling, and Hypertension Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBIntegrins, Vascular Remodeling, and Hypertension Egidius H.J. Heerkens, Ashley S. Izzard and Anthony M. Heagerty Egidius H.J. HeerkensEgidius H.J. Heerkens From the Division of Cardiovascular and Endocrine Sciences, Faculty of Medical and Human Sciences, University of Manchester, United Kingdom. , Ashley S. IzzardAshley S. Izzard From the Division of Cardiovascular and Endocrine Sciences, Faculty of Medical and Human Sciences, University of Manchester, United Kingdom. and Anthony M. HeagertyAnthony M. Heagerty From the Division of Cardiovascular and Endocrine Sciences, Faculty of Medical and Human Sciences, University of Manchester, United Kingdom. Originally published4 Dec 2006https://doi.org/10.1161/01.HYP.0000252753.63224.3bHypertension. 2007;49:1–4Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 4, 2006: Previous Version 1 At the level of the resistance artery, hypertension also brings about a thickening of the vascular wall and inward encroachment on the lumen. This has been reported as being attributable to hypertrophy or hyperplasia of vascular smooth muscle cells (VSMCs), but studies have appeared suggesting that growth is not apparent in arteries at this level of the circulation.1 In addition, detailed structural and mechanical analyses have shown that eutrophic inward remodeling can narrow the vascular lumen without precipitating hypertrophy.2,3 A small amount of hypertrophy may be observed, and in some pathological states, hypertrophy may supervene and is an adverse prognostic sign.4 For the remainder of this section, we consider the reasons why resistance arteries respond to hypertension in this manner.To understand how hypertension produces the above nonhypertrophic changes in small arteries, one must look at the role of the resistance vasculature. At physiological pressures, these vessels typically exhibit a level of contraction (myogenic tone) independent of neurohormonal influences. This response enables blood vessels to constrict or dilate in response to changes in pressure. This process, known as the myogenic response, is only observed in smaller resistance arteries, which mediate autoregulation of blood flow and stabilize capillary pressure.5Hypertrophy is observed in vessels that do not possess myogenic tone, whereas, in smaller resistance arteries, an initial increase in pressure will bring about increased myogenic constriction, which, if prolonged, will lead to inward eutrophic remodeling and/or a reduced arterial distensibility.6 This structural difference between large conduit and resistance arteries is apparent in many models of hypertension, for example, in a hypertensive model bought on by chronic NO synthase inhibition.7 In addition, the magnitude and duration of an increase in intraluminal pressure plays a role in determining the remodeling process.8 It has become evident that the extracellular matrix (ECM) integrin–cytoskeleton axis plays an essential role in the mechanosensory apparatus, which enables VSMCs to detect and respond to changes in intraluminar pressure, allowing eutrophic inward remodeling of resistance arteries in hypertension.Eutrophic Inward RemodelingInward eutrophic remodeling is a process of structural adaptation observed in most forms of hypertension, including the onset of hypertension and milder hypertensive states.9–11 However, a few animal models of hypertension, such as a model developing hypertension independent of the renin–angiotensin system (BPH-2 mice), show hypertrophy as the predominant structural change.12 Inward eutrophic remodeling is a relatively fast functional adaptation observed after prolonged vasoconstriction and is thought to be an energetically favored mechanism to preserve a reduced lumen diameter for long periods.13 The process is also the preferred physiological mechanism by which wall stress can be normalized while maintaining vasomotor tone.14In our studies of the well-characterized TGR(mRen2)27 rat, which develops hypertension from 4 weeks of age, we found that eutrophic inward remodeling occurs from 4 weeks and depends on integrin αVβ3, a multifunctional ECM receptor (Figure 1).9,15 Hypertrophy also begins to appear at between 6 and 8 weeks of age.9 Hypertrophy and a reduced distensibility are also observed in cerebral vessels of the stroke-prone spontaneously hypertensive rat when the animals are given a high-salt/low-protein diet compared with the spontaneously hypertensive rat, before strokes occur.16 The spontaneously hypertensive rat, in contrast, is stroke resistant, and cerebral vessels from young spontaneously hypertensive rats display eutrophic inward remodeling compared with the Wistar-Kyoto rat but exhibit a reduced distensibility in adulthood.3 Finally, subcutaneous small arteries of patients with type 2 diabetes and microalbuminuria exhibit hypertrophy, which coincides with an impaired myogenic response irrespective of whether there is hypertension or not.4,17,18 Therefore, current evidence suggests that an increase of hypertrophy might ensue as a compensatory mechanism8 when eutrophic remodeling is inadequate to normalize wall stress, because the stimulus for remodeling (ie, vasoconstriction) is impaired. Download figureDownload PowerPointFigure 1. VSMC integrins and matrix associations. Integrin α5β1 is the main receptor for fibronectin and mediates the influx of Ca2+ through L-type calcium channels. αVβ3 is a multifunctional integrin receptor that binds to the RGD sequences found in components of the vascular extracellular matrix (vitronectin, ostepontin, and thrombospondin but not von Willebrandt factor, fibrinogen, and sialoprotein which are absent from the smooth muscle extracellular space). αVβ3 is necessary for migration during pressure induced remodeling of arteries.Integrins, Mechanotransduction, and Cytoskeletal ReorganizationThe ECM of resistance arteries is subject to tensile force exerted by blood pressure, which is transferred through integrins across the cell membrane and linked by signaling complexes to the cytoskeleton. Specific integrin subtypes are initially used for mechanotransduction of pressure.19 It has been shown by the use of peptides and specific antibodies that integrins αVβ3 and α5β1 indirectly regulate the myogenic response by control of Ca2+ flow through ion channels. α5β1 is responsible for the initial Ca2+ influx required to establish vessel tone and αVβ3 to mediate force maintenance by a Ca2+ sensitization of contractile components.19–21 These integrins can form complexes that regulate cytoskeletal dynamics to maintain a vascular myogenic force at a given pressure. This is abrogated on cytoskeletal disruption.22,23 Cytoskeletal proteins, such as heat-shock protein 27, activated by RhoA/Rho-kinases, have been shown to regulate myogenic contractility.24 It is now clear that RhoA signaling plays a central role in both calcium sensitization pathways and regulation of actin dynamics in resistance artery remodeling (elegantly reviewed in references25–26). In contrast to molecular signaling mechanisms behind the vascular myogenic response, relatively few data are available on the role of integrins and the underlying biochemical pathways of the next stage of vascular adaptation to hypertension that is the migration of VSMCs toward a narrowed lumen.Integrins and VSMC MigrationRemodeling involves a migratory process after prolonged constriction, whereby existing VSMCs in the vascular wall reposition. A characteristic of migrating cells in vitro is the presence of lamellipodial and filopodial protrusions containing focal adhesion kinases (FAKs), which provide a substrate for other cytosolic proteins, such as Src, and interact with actin-associated cytoplasmic components.27 Evidence for the formation of these structures at the VSMC periphery in resistance arteries is inconclusive. However, it has been shown recently that migration of VSMCs of arteries in vivo is more subtle and limited to elongation of tapered VSMCs and an increase in cell overlap.13 It is thought that cytoskeletal rearrangements and subsequent force generation play a central role in these changes. For example, RhoA is extensively involved in cytosolic actin dynamics, and studies on cultured cells show a complex interaction of the RhoA/Rho kinase–cofilin pathway during cell migration mediated by integrins.28 Elongation and migration of VSMCs, other than resulting in a narrowed lumen, suggest that the change in cell shape, aided by the extracellular environment, would also facilitate an increase in tension generation of VSMCs to counteract increased pressure.29 Whether this mechanism is present in VSMCs of resistance arteries of hypertensive subjects remains unknown, and one should be careful not to equate migratory mechanisms of VSMCs in resistance arteries with those observed in vitro.Integrin αVβ3 is necessary for the pressure-induced inward remodeling process9; however, the biochemical mechanisms underlying this process are sketchy. Src, a component associated with mechanotransduction, is thought to be the initial messenger after integrin activation at the onset of remodeling (Figure 2). It has been shown that elevation of intraluminal pressure of resistance arteries induces Src-Y418 phosphorylation to activate its downstream target FAK, resulting in an accumulation of phosphorylated FAK (Y397).30 Targeting of αV integrins with RGD peptides specifically interferes with FAK activation31 and provides further evidence for a role of Src/FAK pathways in the onset of migration or "sliding" of VSMCs in eutrophic remodeling. Finally, migration of VSMCs in resistance arteries is terminated by fixation of ECM components by surface transglutaminases.32 Transglutaminase is capable of rapidly forming highly stable cross-links of ECM proteins, including collagen, osteopontin, and fibronectin, especially near sites of adhesion, where integrins cluster.33 It is a fast and stable way of fixing cells in place in a remodeled orientation and is replaced over time by gradual matrix turnover.32 One such mechanism by which matrix turnover and stability of other ECM components is facilitated is by fibronectin polymerization into an existing matrix through a caveolin-1–dependent process.34Download figureDownload PowerPointFigure 2. The involvement of vascular smooth muscle integrins in cytoskeletal reorganization during remodeling. Signaling complexes found at the edge of VSMCs in arteries contain integrins, and the cytoplasmic terminal complex (eg, vinculin, paxillin, talin, and p130Cas) associate with the actin cytoskeleton. Src and FAK in arteries are phosphorylated on integrin engagement and are essential in the actin (dis)assembly possibly regulated by RhoA/Rho-kinases. Permanent placement of VSMCs in the remodeled vasculature involves tissue-transglutaminase (tTG) fixation.PerspectivesA central role for integrins seems to have been clearly established when it comes to the maintenance of myogenic integrity in the resistance vasculature. The breakdown of autoregulation and the loss of a physiological myogenic response to pressure seems to be involved in increasing pathological blood flow to target organs with the resulting loss of cellular function and tissue damage. It remains uncertain as to whether correction of hypertension is inevitably associated with the restoration of the myogenic response or complete protection of vital organs. Data from the vasculature of normotensive diabetics would suggest that this is not the case. The specific identification of 2 integrins that seem to have a crucial role in not only maintaining adequate myogenicity but also being responsible for the physiological response to pressure, namely, eutrophic inward remodeling, means that there is the tantalizing possibility of developing new therapeutic molecules to enhance their activity, thereby reinforcing the physiological responses to pressure, namely, eutrophic remodeling and the ability to respond to high-pressure loads with vasoconstriction. In addition to conventional antihypertensive therapy, it may well be that the future of blood pressure treatment centers around maintaining normal vascular function in this way.We thank Maureen Speed for her assistance in preparing this work.Sources of Funding.We thank the Wellcome Trust and British Heart Foundation for supporting our research. Our clinical studies are carried out in the Manchester Wellcome Trust Clinical Research Facility.DisclosuresNone.FootnotesCorrespondence to Anthony M. Heagerty, Division of Cardiovascular and Endocrine Sciences, Faculty of Medical and Human Sciences, University of Manchester, Core Technology Facility, 46 Grafton St, Manchester, M13 9NT United Kingdom. E-mail [email protected] References 1 Heagerty AM, Aalkjaer C, Bund SJ, Korsgaard N, Mulvany MJ. Small artery structure in hypertension. Dual processes of remodeling and growth. Hypertension. 1993; 21: 391–397.LinkGoogle Scholar2 Thybo NK, Stephens N, Cooper A, Aalkjaer C, Heagerty AM, Mulvany MJ. Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension. 1995; 25: 474–481.CrossrefMedlineGoogle Scholar3 Izzard AS, Horton S, Heerkens EH, Shaw L, Heagerty AM. Middle cerebral artery structure and distensibility during developing and established phases of hypertension in the spontaneously hypertensive rat. J Hypertens. 2006; 24: 875–880.CrossrefMedlineGoogle Scholar4 Izzard AS, Rizzoni D, Agabiti-Rosei E, Heagerty AM. Small artery structure and hypertension: adaptive changes and target organ damage. J Hypertens. 2005; 23: 247–250.CrossrefMedlineGoogle Scholar5 Osol G, Osol R, Halpern W. Pre-existing level of tone is an important determinant of cerebral artery autoregulatory responsiveness. J Hypertens. 1989; 7 (suppl): S67–S69.Google Scholar6 Dunn WR, Wallis SJ, Gardiner SM. Remodelling and enhanced myogenic tone in cerebral resistance arteries isolated from genetically hypertensive Brattleboro rats. J Vasc Res. 1998; 35: 18–26.CrossrefMedlineGoogle Scholar7 Bouvet C, Gilbert LA, Girardot D, deBlois D, Moreau P. Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition. Hypertension. 2005; 45: 432–437.LinkGoogle Scholar8 Pries AR, Reglin B, Secomb TW. Remodeling of blood vessels: responses of diameter and wall thickness to hemodynamic and metabolic stimuli. Hypertension. 2005; 46: 725–731.LinkGoogle Scholar9 Heerkens EH, Shaw L, Ryding A, Brooker G, Mullins JJ, Austin C, Ohanian V, Heagerty AM. alphaV integrins are necessary for eutrophic inward remodeling of small arteries in hypertension. Hypertension. 2006; 47: 281–287.LinkGoogle Scholar10 Korsgaard N, Aalkjaer C, Heagerty AM, Izzard AS, Mulvany MJ. Histology of subcutaneous small arteries from patients with essential hypertension. Hypertension. 1993; 22: 523–526.LinkGoogle Scholar11 Li JS, Knafo L, Turgeon A, Garcia R, Schiffrin EL. Effect of endothelin antagonism on blood pressure and vascular structure in renovascular hypertensive rats. Am J Physiol. 1996; 271: H88–H93.MedlineGoogle Scholar12 Baumbach GL, Sigmund CD, Faraci FM. Cerebral arteriolar structure in mice overexpressing human renin and angiotensinogen. Hypertension. 2003; 41: 50–55.LinkGoogle Scholar13 Martinez-Lemus LA, Hill MA, Bolz SS, Pohl U, Meininger GA. Acute mechanoadaptation of vascular smooth muscle cells in response to continuous arteriolar vasoconstriction: implications for functional remodeling. FASEB J. 2004; 18: 708–710.CrossrefMedlineGoogle Scholar14 Mulvany MJ. Abnormalities of the resistance vasculature in hypertension: correction by vasodilator therapy. Pharmacol Rep. 2005; 57 (suppl): 144–150.MedlineGoogle Scholar15 Thybo NK, Korsgaard N, Mulvany MJ. Morphology and function of mesenteric resistance arteries in transgenic rats with low-renin hypertension. J Hypertens. 1992; 10: 1191–1196.CrossrefMedlineGoogle Scholar16 Izzard AS, Graham D, Burnham MP, Heerkens EH, Dominiczak AF, Heagerty AM. Myogenic and structural properties of cerebral arteries from the stroke-prone spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2003; 285: H1489–H1494.CrossrefMedlineGoogle Scholar17 Endemann DH, Pu Q, De Ciuceis C, Savoia C, Virdis A, Neves MF, Touyz RM, Schiffrin EL. Persistent remodeling of resistance arteries in type 2 diabetic patients on antihypertensive treatment. Hypertension. 2004; 43: 399–404.LinkGoogle Scholar18 Schofield I, Malik R, Izzard A, Austin C, Heagerty A. Vascular structural and functional changes in type 2 diabetes mellitus: evidence for the roles of abnormal myogenic responsiveness and dyslipidemia. Circulation. 2002; 106: 3037–3043.LinkGoogle Scholar19 Martinez-Lemus LA, Sun Z, Trache A, Trzciakowski JP, Meininger GA. Integrins and regulation of the microcirculation: from arterioles to molecular studies using atomic force microscopy. Microcirculation. 2005; 12: 99–112.CrossrefMedlineGoogle Scholar20 Wu X, Mogford JE, Platts SH, Davis GE, Meininger GA, Davis MJ. Modulation of calcium current in arteriolar smooth muscle by alphav beta3 and alpha5 beta1 integrin ligands. J Cell Biol. 1998; 143: 241–252.CrossrefMedlineGoogle Scholar21 Wu X, Davis GE, Meininger GA, Wilson E, Davis MJ. Regulation of the L-type calcium channel by alpha 5beta 1 integrin requires signaling between focal adhesion proteins. J Biol Chem. 2001; 276: 30285–30292.CrossrefMedlineGoogle Scholar22 Cipolla MJ, Gokina NI, Osol G. Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior. FASEB J. 2002; 16: 72–76.CrossrefMedlineGoogle Scholar23 Flavahan NA, Bailey SR, Flavahan WA, Mitra S, Flavahan S. Imaging remodeling of the actin cytoskeleton in vascular smooth muscle cells after mechanosensitive arteriolar constriction. Am J Physiol. 2005; 288: H660–H669.CrossrefMedlineGoogle Scholar24 Dubroca C, You D, Levy BI, Loufrani L, Henrion D. Involvement of RhoA/Rho kinase pathway in myogenic tone in the rabbit facial vein. Hypertension. 2005; 45: 974–979.LinkGoogle Scholar25 Lee DL, Webb RC, Jin L. Hypertension and RhoA/Rho-kinase signaling in the vasculature: highlights from the recent literature. Hypertension. 2004; 44: 796–799.LinkGoogle Scholar26 Loirand G, Rolli-Derkinderen M, Pacaud P. RhoA and resistance artery remodeling. Am J Physiol. 2005; 288: H1051–H1056.CrossrefMedlineGoogle Scholar27 Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol. 2005; 6: 56–68.CrossrefMedlineGoogle Scholar28 Danen EH, van Rheenen J, Franken W, Huveneers S, Sonneveld P, Jalink K, Sonnenberg A. Integrins control motile strategy through a Rho-cofilin pathway. J Cell Biol. 2005; 169: 515–526.CrossrefMedlineGoogle Scholar29 Polte TR, Eichler GS, Wang N, Ingber DE. Extracellular matrix controls myosin light chain phosphorylation and cell contractility through modulation of cell shape and cytoskeletal prestress. Am J Physiol Cell Physiol. 2004; 286: C518–C528.CrossrefMedlineGoogle Scholar30 Rice DC, Dobrian AD, Schriver SD, Prewitt RL. Src autophosphorylation is an early event in pressure-mediated signaling pathways in isolated resistance arteries. Hypertension. 2002; 39: 502–507.CrossrefMedlineGoogle Scholar31 Varadarajulu J, Laser M, Hupp M, Wu R, Hauck CR. Targeting of alpha(v) integrins interferes with FAK activation and smooth muscle cell migration and invasion. Biochem Biophys Res Commun. 2005; 331: 404–412.CrossrefMedlineGoogle Scholar32 Bakker EN, Buus CL, Spaan JA, Perree J, Ganga A, Rolf TM, Sorop O, Bramsen LH, Mulvany MJ, Vanbavel E. Small artery remodeling depends on tissue-type transglutaminase. Circ Res. 2005; 96: 119–126.LinkGoogle Scholar33 Langille BL, Dajnowiec D. Cross-linking vasomotor tone and vascular remodeling: a novel function for tissue transglutaminase? Circ Res. 2005; 96: 9–11.LinkGoogle Scholar34 Sottile J, Chandler J. Fibronectin matrix turnover occurs through a caveolin-1-dependent process. Mol Biol Cell. 2005; 16: 757–768.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Davis M, Earley S, Li Y and Chien S (2023) Vascular mechanotransduction, Physiological Reviews, 10.1152/physrev.00053.2021, 103:2, (1247-1421), Online publication date: 1-Apr-2023. Rachev A and Shazly T (2022) A Mathematical Model of Maladaptive Inward Eutrophic Remodeling of Muscular Arteries in Hypertension, Journal of Biomechanical Engineering, 10.1115/1.4055109, 145:1, Online publication date: 1-Jan-2023. Rizzoni D, Agabiti-Rosei C and De Ciuceis C (2022) State of the Art Review: Vascular Remodeling in Hypertension, American Journal of Hypertension, 10.1093/ajh/hpac093, 36:1, (1-13), Online publication date: 1-Jan-2023. Liu Y, Duan Y, Zhao N, Zhu X, Yu X, Jiao S, Song Y, Shi L, Ma Y, Wang X, Yu B and Qu A (2022) Peroxisome Proliferator-Activated Receptor α Attenuates Hypertensive Vascular Remodeling by Protecting Vascular Smooth Muscle Cells from Angiotensin II-Induced ROS Production, Antioxidants, 10.3390/antiox11122378, 11:12, (2378) Arishe O, Priviero F, Wilczynski S and Webb R (2021) Exosomes as Intercellular Messengers in Hypertension, International Journal of Molecular Sciences, 10.3390/ijms222111685, 22:21, (11685) de Wit C (2021) Mechanobiology of Arterial Hypertension Vascular Mechanobiology in Physiology and Disease, 10.1007/978-3-030-63164-2_10, (277-298), . Lee S, Jeong M, Sung J, Yeon H, Chang J and Lim H (2019) Effect of remifentanil infusion on the hemodynamic response during induction of anesthesia in hypertensive and normotensive patients: a prospective observational study, Journal of International Medical Research, 10.1177/0300060519883568, 47:12, (6254-6267), Online publication date: 1-Dec-2019. Arnold C, Feldner A, Zappe M, Komljenovic D, De La Torre C, Ruzicka P, Hecker M, Neuhofer W and Korff T (2018) Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow‐ and pressure‐induced arterial remodeling in mice, The FASEB Journal, 10.1096/fj.201801594R, 33:3, (3364-3377), Online publication date: 1-Mar-2019. Shaheen S, Wan Z, Haneef K, Zeng Y, Jing W and Liu W (2019) B cell mechanosensing: A mechanistic overview Advances in Immunology in China - Part A, 10.1016/bs.ai.2019.08.003, (23-63), . Mahavadi S, Nalli A, Wang H, Kendig D, Crowe M, Lyall V, Grider J, Murthy K and Manser E (2018) Regulation of gastric smooth muscle contraction via Ca2+-dependent and Ca2+-independent actin polymerization, PLOS ONE, 10.1371/journal.pone.0209359, 13:12, (e0209359) Favero G, Paini A, De Ciuceis C, Rodella L, Moretti E, Porteri E, Rossini C, Ministrini S, Solaini L, Stefano C, Coschignano M, Brami V, Petelca A, Nardin M, Valli I, Tiberio G, Bonomini F, Agabiti Rosei C, Portolani N, Rizzoni D and Rezzani R (2018) Changes in extracellular matrix in subcutaneous small resistance arteries of patients with essential hypertension, Blood Pressure, 10.1080/08037051.2018.1448256, 27:4, (231-239), Online publication date: 4-Jul-2018. Frismantiene A, Kyriakakis E, Dasen B, Erne P, Resink T and Philippova M (2017) Actin cytoskeleton regulates functional anchorage-migration switch during T-cadherin-induced phenotype modulation of vascular smooth muscle cells, Cell Adhesion & Migration, 10.1080/19336918.2017.1319545, 12:1, (69-85), Online publication date: 2-Jan-2018. Agabiti-Rosei E and Rizzoni D (2017) Microvascular structure as a prognostically relevant endpoint, Journal of Hypertension, 10.1097/HJH.0000000000001259, 35:5, (914-921), Online publication date: 1-May-2017. Lee R, Dickhout J and Sandow S (2016) Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance, Hypertension Research, 10.1038/hr.2016.145, 40:4, (311-323), Online publication date: 1-Apr-2017. Ribas J, Zhang Y, Pitrez P, Leijten J, Miscuglio M, Rouwkema J, Dokmeci M, Nissan X, Ferreira L and Khademhosseini A (2017) Biomechanical Strain Exacerbates Inflammation on a Progeria‐on‐a‐Chip Model, Small, 10.1002/smll.201603737, 13:15, (1603737), Online publication date: 1-Apr-2017. Hellsten Y and Nyberg M (2015) Cardiovascular Adaptations to Exercise Training Comprehensive Physiology, 10.1002/cphy.c140080, (1-32) Zhuo Y, Qian T, Wu Y, Seong J, Gong Y, Ma H, Wang Y and Lu S (2015) Subcellular and Dynamic Coordination between Src Activity and Cell Protrusion in Microenvironment, Scientific Reports, 10.1038/srep12963, 5:1, Online publication date: 1-Oct-2015. Taghizadeh H, Tafazzoli-Shadpour M and Shadmehr M (2015) Analysis of arterial wall remodeling in hypertension based on lamellar modeling, Journal of the American Society of Hypertension, 10.1016/j.jash.2015.07.014, 9:9, (735-744), Online publication date: 1-Sep-2015. Fediuk J and Dakshinamurti S (2015) A role for actin polymerization in persistent pulmonary hypertension of the newborn, Canadian Journal of Physiology and Pharmacology, 10.1139/cjpp-2014-0413, 93:3, (185-194), Online publication date: 1-Mar-2015. Staiculescu M, Foote C, Meininger G and Martinez-Lemus L (2014) The Role of Reactive Oxygen Species in Microvascular Remodeling, International Journal of Molecular Sciences, 10.3390/ijms151223792, 15:12, (23792-23835) Arnold C, Feldner A, Pfisterer L, Hödebeck M, Troidl K, Genové G, Wieland T, Hecker M and Korff T (2014) RGS 5 promotes arterial growth during arteriogenesis , EMBO Molecular Medicine, 10.15252/emmm.201403864, 6:8, (1075-1089), Online publication date: 1-Aug-2014. Castorena-Gonzalez J, Staiculescu M, Foote C and Martinez-Lemus L (2014) Mechanisms of the Inward Remodeling Process in Resistance Vessels: Is the Actin Cytoskeleton Involved?, Microcirculation, 10.1111/micc.12105, 21:3, (219-229), Online publication date: 1-Apr-2014. Scherer C, Pfisterer L, Wagner A, Hödebeck M, Cattaruzza M, Hecker M and Korff T (2014) Arterial Wall Stress Controls NFAT5 Activity in Vascular Smooth Muscle Cells, Journal of the American Heart Association, 3:2, Online publication date: 24-Mar-2014. Gliemann L, Nyberg M and Hellsten Y (2013) Nitric oxide and reactive oxygen species in limb vascular function: what is the effect of physical activity?, Free Radical Research, 10.3109/10715762.2013.835045, 48:1, (71-83), Online publication date: 1-Jan-2014. Heerkens E, Quinn L, Withers S and Heagerty A (2014) β Integrins Mediate FAK Y397 Autophosphorylation of Resistance Arteries during Eutrophic Inward Remodeling in Hypertension, Journal of Vascular Research, 10.1159/000365479, 51:4, (305-314), . Khavandi K, Arunakirinathan M, Greenstein A and Heagerty A (2013) Retinal Arterial Hypertrophy: the New LVH?, Current Hypertension Reports, 10.1007/s11906-013-0347-2, 15:3, (244-252), Online publication date: 1-Jun-2013. Pfisterer L, Feldner A, Hecker M and Korff T (2012) Hypertension impairs myocardin function: a novel mechanism facilitating arterial remodelling, Cardiovascular Research, 10.1093/cvr/cvs247, 96:1, (120-129), Online publication date: 1-Oct-2012., Online publication date: 1-Oct-2012. Yamin R and Morgan K (2012) Deciphering actin cytoskeletal function in the contractile vascular smooth muscle cell, The Journal of Physiology, 10.1113/jphysiol.2012.232306, 590:17, (4145-4154), Online publication date: 1-Sep-2012. Nyberg M, Jensen L, Thaning P, Hellsten Y and Mortensen S (2012) Role of nitric oxide and prostanoids in the regulation of leg blood flow and blood pressure in humans with essential hypertension: effect of high-intensity aerobic training, The Journal of Physiology, 10.1113/jphysiol.2011.225136, 590:6, (1481-1494), Online publication date: 1-Mar-2012. Martinez-Lemus L (2011) The Dynamic Structure of Arterioles, Basic & Clinical Pharmacology & Toxicology, 10.1111/j.1742-7843.2011.00813.x, 110:1, (5-11), Online publication date: 1-Jan-2012. Rizzoni D, De Ciuceis C, Porteri E, Semeraro F and Rosei E (2011) Structural Alterations in Small Resistance Arteries in Obesity, Basic & Clinical Pharmacology & Toxicology, 10.1111/j.1742-7843.2011.00786.x, 110:1, (56-62), Online publication date: 1-Jan-2012. Chao J and Davis M (2011) The Roles of Integrins in Mediating the Effects of Mechanical Force and Growth Factors on Blood Vessels in Hypertension, Current Hypertension Reports, 10.1007/s11906-011-0227-6, 13:6, (421-429), Online publication date: 1-Dec-2011. Yu J, Zhou R and Cai G (2011) From Hypertension to Stroke: Mechanisms and Potential Prevention Strategies, CNS Neuroscience & Therapeutics, 10.1111/j.1755-5949.2011.00264.x, 17:5, (577-584), Online publication date: 1-Oct-2011. Safar M, Blacher J and Jankowski P (2011) Arterial stiffness, pulse pressure, and cardiovascular disease—Is it possible to break the vicious circle?, Atherosclerosis, 10.1016/j.atherosclerosis.2011.04.039, 218:2, (263-271), Online publication date: 1-Oct-2011. De Ciuceis C, Porteri E, Rizzoni D, Corbellini C, La Boria E, Boari G, Pilu A, Mittempergher F, Di Betta E, Casella C, Nascimbeni R, Rosei C, Ruggeri G, Caimi L and Rosei E (2011) Effects of Weight Loss
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