Expression of Soluble and Insoluble Fibronectin in Rat Aorta: Effects of Angiotensin II and Endothelin-1

Hahn, Alfred W.A.; Regenass, Stephan; Kern, Frances; Fr, Bühler; Resink, Thérèse J.

doi:10.1006/bbrc.1993.1399

Cited by 35 publications

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“…Activation of the RAS has previously been shown to induce multiple growth factors that have been implicated in fibrosis, such as transforming growth factor-␤ (TGF-␤) and platelet-derived growth factor-␤ (46 -48). Induction of these growth factors appears to be mediated by Ang II acting at the AT1 receptor (49). TGF-␤ itself is known to regulate PAI-1 gene expression through the Smad-dependent signaling pathway (50).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Inhibits Human Trophoblast Invasion through AT1 Receptor Activation

Xia

Wen

Kellems

2002

Journal of Biological Chemistry

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Trophoblast implantation depends, in part, on the controlled production of plasmin from plasminogen, a process regulated by plasminogen activators and plasminogen activator inhibitors. We have determined that angiotensin II (Ang II) stimulates plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in human trophoblasts in a time-and concentration-dependent manner. Our results indicate that Ang II activates PAI-1 gene expression through the AT1 receptor and involves the calcium-dependent activation of calcineurin and the nuclear translocation of NFAT. Increased PAI-1 synthesis and secretion is associated with reduced trophoblast invasion as judged by an in vitro invasion assay. These studies are the first to link the renin-angiotensin system with the fibrinolytic system to regulate trophoblast invasion.The fibrinolytic system is best known for its role in the regulated digestion of fibrin clots. A key component of this system is plasminogen, an inactive zymogen, which is converted into the active protease, plasmin, by the action of a plasminogen activator termed tissue-type plasminogen activator (tPA).1 The ability of tPA to activate plasminogen is substantially enhanced by its association with the substrate, fibrin (1). Plasminogen can also be activated (i.e. converted to plasmin) by the action of another plasminogen activator, urokinase-type plasminogen activator (uPA) (2-6). In contrast to tPA, uPA is not associated with fibrin clots but instead is often associated with a specific cell surface receptor (uPAR) (7), which is thought to play a key role in cell migration and invasion (8). In this role, uPA is synthesized as an inactive single-chain proenzyme that can be stored or secreted. Secreted uPA is cleaved into the active two-chain molecule upon binding to uPAR on the surface of cells. Following activation, receptorbound uPA is capable of converting plasminogen into plasmin, the latter of which is able to degrade several key components of the extracellular matrix (ECM) (9). It is widely accepted that uPA initiates a cascade of proteolysis at the cell surface, which in turn leads to the degradation of the ECM, thereby promoting cellular migration. It is now clear that the uPA-regulated aspect of the fibrinolytic system plays a key role in mediating ECM degradation and cell invasion. Plasminogen activator activity is controlled by plasminogen activator inhibitors (PAIs) of which PAI-1 is the predominant physiological inhibitor (1, 10, 11). PAI-1 is an ECM glycoprotein that is capable of inhibiting both free and receptor-bound uPA through the formation of an irreversible covalent complex (12). In this way PAI-1 is believed to control cell migration and invasion in tumor growth and angiogenesis (13-16).Numerous studies suggest that PAI-1 production by human trophoblasts plays an important role in trophoblast invasion and placental development (17, 18). The human hemochorial placenta is a highly invasive structure in which a subpopulation of placental trophoblast cells invades the uterus, its underlyi...

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Section: Discussionmentioning

confidence: 99%

Angiotensin II Inhibits Human Trophoblast Invasion through AT1 Receptor Activation

Xia

Wen

Kellems

2002

Journal of Biological Chemistry

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“…Endothelin, which is stimulated by Aldo, 4,21 has been also demonstrated to induce the expression of vascular Fn. 22 Recent work by Ammarguellat et al 23 shows that cardiac fibronectin is increased in DOCA-salt rats and that this increase is prevented by administration of an endothelin type A receptor antagonist. These findings suggest that elevated Aldo may promote Fn production within the media independently of AP through increased synthesis of endogenous endothelin.…”

Section: Arterial Wall Hypertrophy and Compositionmentioning

confidence: 99%

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

et al. 2002

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Background-Previous studies have demonstrated the development of cardiac fibrosis in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on in vivo mechanical properties of the carotid artery using echo-tracking system. Methods and Results-Aldo was administered (1 g/h) in uninephrectomized Sprague-Dawley rats (SD) receiving a high-salt diet from 8 to 12 weeks of age. Uninephrectomized control SD rats received a normal salt diet without Aldo. Three groups of Aldo-salt rats were treated with 1, 10, or 30 mg/kg Ϫ1 · d Ϫ1 of Epl by gavage. Elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The structure of the arterial wall was analyzed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo produced increased systolic arterial pressure, pulse pressure, Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities compared with controls without Aldo. No differences in collagen mRNA levels were detected between groups. Epl blunted the increase in pulse pressure in Aldo rats and normalized Einc-wall stress curves, MCSA, and EIIIA Fn. These effects were dose dependent and not accompanied by a reduction in wall stress. Conclusions-Aldo is able to increase arterial stiffness associated with Fn accumulation, independently of wall stress. The preventive effects of Epl suggest a direct role for mineralocorticoid receptors in mechanical and structural alterations of large vessels in rat hyperaldosteronism.

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“…The atherogenicity of angII has been ascribed to several effects of angII, including its proinflammatory properties and its effect in stimulating the proliferation of vascular smooth muscle cells (6,7). AngII is known to stimulate the secretion of extracellular matrix (ECM) components by vascular smooth muscle cells, such as laminin, fibronectin, collagen, elastin, and proteoglycans (8)(9)(10)(11)(12). However, it is not known whether this stimulation of ECM components leads to increased LDL retention in the artery wall.…”

mentioning

confidence: 99%

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

Huang

Thompson

Wilson

et al. 2008

Journal of Lipid Research

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Angiotensin II (angII) is known to promote atherosclerosis; however, the mechanisms involved are not fully understood. To determine whether angII stimulates proteoglycan production and LDL retention, LDL receptordeficient mice were infused with angII (1,000 ng/kg/min) or saline via osmotic minipumps. To control for the hypertensive effect of angII, a parallel group received norepinephrine (NE; 5.6 mg/kg/day). Arterial lipid accumulation was evaluated by measuring the retention rate of LDL in isolated carotid arteries perfused ex vivo. Mice infused with angII had increased vascular content of biglycan and perlecan and retained twice as much LDL as saline-or NEinfused mice, although no group developed atherosclerosis at this time. To determine whether this increase in biglycan and perlecan content predisposed to atherosclerosis development, mice were infused with angII, saline, or NE for 4 weeks, then pumps were removed and mice received an atherogenic Western diet for another 6 weeks. Mice that had received angII infusions had 3-fold increased atherosclerosis compared with mice that had received saline or NE, and apolipoprotein B colocalized with both proteoglycans. Thus, one mechanism by which angII promotes atherosclerosis is increased proteoglycan synthesis and increased arterial LDL retention, which precedes and contributes to atherosclerosis

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Expression of Soluble and Insoluble Fibronectin in Rat Aorta: Effects of Angiotensin II and Endothelin-1

Cited by 35 publications

References 0 publications

Angiotensin II Inhibits Human Trophoblast Invasion through AT1 Receptor Activation

Angiotensin II Inhibits Human Trophoblast Invasion through AT1 Receptor Activation

Increased Carotid Wall Elastic Modulus and Fibronectin in Aldosterone-Salt–Treated Rats

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development

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