Angiotensin II AT<sub>2</sub> receptor inhibits smooth muscle cell  migration via fibronectin cell production and binding

Chassagne, Catherine; Adamy, C.; Ratajczak, Philippe; Gingras, Bruno; Teiger, Emmanuel; Planus, Emmanuelle; Oliviéro, P.; Rappaport, L.; Samuel, Jane‐Lise; Meloche, Sylvain

doi:10.1152/ajpcell.00318.2001

Cited by 20 publications

(8 citation statements)

References 61 publications

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“…This occurred despite significant increase in fibronectin, which we demonstrated is modulated by AT 2 receptors. 18 In support of our findings, Chassagne et al 32 demonstrated that AT 2 receptor activation inhibited VSMC migration through fibronectin secretion and subsequent VSMC attachment. It is therefore possible that ␣ 5 subunit expression, which can mediate cell attachment to fibronectin, is associated with a nonmigratory VSMC phenotype.…”

Section: Discussionsupporting

confidence: 88%

Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II–Infused Rats

et al. 2006

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Abstract-Angiotensin II plays an important role in vascular remodeling through effects that involve, in part, interactions of vascular smooth muscle cells with extracellular matrix via integrins, which belong to a family of transmembrane receptors. We hypothesized that angiotensin (Ang) II regulates expression of vascular integrins and their ligands in experimental hypertension. Rats were infused subcutaneously with Ang II and received angiotensin type-1 (AT 1 ) receptor blocker losartan, the AT 1 /angiotensin type-2 (AT 2 ) [Sar 1 -Ile 8 ]-Ang II, or the vasodilator hydralazine for 7 days. Osteopontin and integrin subunit expression were evaluated immunohistochemically. Ang II enhanced vascular ␣ 8 , ␤ 1 , ␤ 3 integrins and osteopontin expression, which were significantly reduced by losartan, [Sar 1 -Ile 8 ]-Ang II, and hydralazine. Although Ang II increased vascular ␣ 5 subunit expression, this was additionally increased by losartan. Losartan was the only treatment that induced ␣ 1 subunit expression. These results demonstrate that AT 1 and AT 2 receptors have countervailing effects on vascular integrin subunit expression that may influence their effects on vascular remodeling and extracellular matrix composition. Key Words: renin-angiotensin system Ⅲ aorta Ⅲ extracellular matrix Ⅲ hypertension Ⅲ osteopontin M igration of vascular smooth muscle cells (VSMCs) within or from the media to the intima plays a major role in arterial remodeling in atherosclerosis and hypertension. Migration of VSMCs and remodeling require controlled degradation of extracellular matrix (ECM) proteins by matrix metalloproteinases (MMPs) and the activation or release of growth factors. VSMCs are embedded in ECM that includes collagens, fibronectin, laminin, elastin, and proteoglycans. 1 The composition of the ECM can change in response to vascular injury. For example, the ECM protein tenascin, absent in normal rat aortic media, is expressed in the neointima in hypertension or after injury. 2,3 Several receptor-ligand systems, such as integrins, are involved in cell-ECM interactions, which regulate cell phenotype and function. Integrins belong to a superfamily of transmembrane glycoprotein adhesion receptors consisting of 2 noncovalently linked subunits, ␣ and ␤. To date, at least 18 ␣ subunits and 8 ␤ subunits have been described, with a resulting combination of Ͼ22 integrins with varying ligand specificity. 4 The surrounding ECM, as well as integrinmatrix interactions, regulate a variety of cell behaviors, including migration, 5,6 proliferation, 7 proteinase production, and differentiation. 8 -10 During the processes of VSMC migration from the media to the intima, cells dissociate from and degrade the ECM proteins. This process involves 3 steps: a phenotypic change from the contractile to the synthetic state, proteolysis of ECM proteins, and cell migration through matrix digestion, a process that resembles tumor cell invasion. 11 Remodeling of the small arteries occurs in both human and experimental models of hypertension and involve...

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Section: Discussionsupporting

confidence: 88%

Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II–Infused Rats

et al. 2006

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“…Another possible atheroprotective mechanism of AT 1 R blockade could be that ''free'' AngII could bind to the AT 2 R. Stimulation of the AT 2 R has been shown to inhibit neo-intimal formation (Janiak et al 1992), decrease smooth muscle cell proliferation (Nakajima et al 1995) and migration (Chassagne et al 2002), and inhibit fibroblast proliferation (Tsuzuki et al 1996). Moreover, AngII can be converted to Ang (1-7) by ACE2 (Boehm and Nabel 2002).…”

Section: Discussionmentioning

confidence: 99%

Immunolocalization of ACE2 and AT₂ Receptors in Rabbit Atherosclerotic Plaques

Zulli

Burrell

Widdop

et al. 2006

J Histochem Cytochem.

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S U M M A R Y Evidence suggests that angiotensin type 2 receptor (AT 2 R) and angiotensinconverting enzyme 2 (ACE2) play a protective role in atherogenesis. These factors have not been identified in rabbit atherosclerotic plaques. Our goal was to localize ACE2 and AT 2 R in rabbit atherosclerotic tissues, and determine which cell types express these factors. New Zealand White rabbits were fed either a control diet or a 0.5% cholesterol diet (n58/group) for 12 weeks. Paraffin-fixed thoracic aorta were serially sectioned and processed for immunohistochemistry using commercially available antibodies to ACE2, AT 2 R, RAM 11 (to identify macrophages), and a smooth muscle cell actin (aSMC) to identify smooth muscle cells and myofibroblasts. AT 2 R immunoreactivity, but not ACE2 immunoreactivity, was clearly present in endothelia overlying normal wall. However, both AT 2 R and ACE2 immunoreactivity were clearly present in endothelia overlying neo-intima formation and atherosclerotic plaques. Within plaques, both AT 2 R and ACE2 immunoreactivity were observed in macrophages and aSMC actin-positive cells. Examination of serial sections showed that the majority of cells were both ACE2-and AT 2 R-positive. Macrophages and aSMC actin-positive cells produce ACE2 and the AT 2 R in atherosclerotic plaques. Determining a role for these factors in the control of atherosclerosis will require additional studies.

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“…88 Ang-II may also inhibit SMC migration through the AT2 receptor by increasing cellular FN synthesis and associated cell binding. 89 IGF-1, a small polypeptide with structural homology to proinsulin, is produced by many cell types and acts as an autocrine/paracrine growth factor. It has been postulated to play a role in SMC growth in the bladder, uterus, and vasculature.…”

Section: Molecular Regulation Of Contractile Smooth Muscle Cell Phenomentioning

confidence: 99%

Molecular Regulation of Contractile Smooth Muscle Cell Phenotype: Implications for Vascular Tissue Engineering

Beamish

Kottke‐Marchant

et al. 2010

Tissue Engineering Part B: Reviews

324

331

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The molecular regulation of smooth muscle cell (SMC) behavior is reviewed, with particular emphasis on stimuli that promote the contractile phenotype. SMCs can shift reversibly along a continuum from a quiescent, contractile phenotype to a synthetic phenotype, which is characterized by proliferation and extracellular matrix (ECM) synthesis. This phenotypic plasticity can be harnessed for tissue engineering. Cultured synthetic SMCs have been used to engineer smooth muscle tissues with organized ECM and cell populations. However, returning SMCs to a contractile phenotype remains a key challenge. This review will integrate recent work on how soluble signaling factors, ECM, mechanical stimulation, and other cells contribute to the regulation of contractile SMC phenotype. The signal transduction pathways and mechanisms of gene expression induced by these stimuli are beginning to be elucidated and provide useful information for the quantitative analysis of SMC phenotype in engineered tissues. Progress in the development of tissue-engineered scaffold systems that implement biochemical, mechanical, or novel polymer fabrication approaches to promote contractile phenotype will also be reviewed. The application of an improved molecular understanding of SMC biology will facilitate the design of more potent cell-instructive scaffold systems to regulate SMC behavior.

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Angiotensin II AT₂ receptor inhibits smooth muscle cell migration via fibronectin cell production and binding

Cited by 20 publications

References 61 publications

Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II–Infused Rats

Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II–Infused Rats

Immunolocalization of ACE2 and AT₂ Receptors in Rabbit Atherosclerotic Plaques

Molecular Regulation of Contractile Smooth Muscle Cell Phenotype: Implications for Vascular Tissue Engineering

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Angiotensin II AT2 receptor inhibits smooth muscle cell migration via fibronectin cell production and binding

Cited by 20 publications

References 61 publications

Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II–Infused Rats

Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II–Infused Rats

Immunolocalization of ACE2 and AT2 Receptors in Rabbit Atherosclerotic Plaques

Molecular Regulation of Contractile Smooth Muscle Cell Phenotype: Implications for Vascular Tissue Engineering

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Product

Resources

About

Angiotensin II AT₂ receptor inhibits smooth muscle cell migration via fibronectin cell production and binding

Immunolocalization of ACE2 and AT₂ Receptors in Rabbit Atherosclerotic Plaques