Fibronectin biosynthesis in the rat aorta in vitro. Changes due to experimental hypertension.

Saouaf, Rola; Takasaki, Izumi; Eastman, Eric; Chobanian, Aram V.; Brecher, Peter

doi:10.1172/jci115420

Cited by 37 publications

(19 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10,16,20 The Aldo-salt model represents the first demonstration of the functional role of Fn in arterial elasticity without any increase in mechanical wall stress. A previous study 15 showing that EIIIA Fn synthesis was increased in aortic rings from rats treated with deoxycorticosterone/salt suggests that mineralocorticoids may be implicated in Fn accumulation in vessels. The increase in Fn expression was specific, because it was not associated with a concomitant increase in collagen expression.…”

Section: Arterial Wall Hypertrophy and Compositionmentioning

confidence: 85%

“…Previous reports have shown that high level of mechanical stress, 15,16 stimulation of the renin angiotensin system, 17,18 as well as high sodium intake 14,19 may stimulate Fn synthesis. Because in these studies the level of wall stress was high, it is difficult to distinguish its role from that of sodium or renin angiotensin system.…”

Section: Arterial Wall Hypertrophy and Compositionmentioning

confidence: 96%

See 1 more Smart Citation

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

et al. 2002

View full text Add to dashboard Cite

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.

show abstract

Section: Arterial Wall Hypertrophy and Compositionmentioning

confidence: 85%

Section: Arterial Wall Hypertrophy and Compositionmentioning

confidence: 96%

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

et al. 2002

View full text Add to dashboard Cite

show abstract

“…16 In addition, FN expression in the rat aorta increases with age and hypertension. [17][18][19] We hypothesized that accumulation of FN and its receptor may play a role in the regulation of elastic properties of large arteries during chronic hypertension.Our objectives were to determine (1) the intrinsic elastic properties of the arterial wall by evaluating the relationship between the E inc and circumferential wall stress under in vivo conditions and (2) the changes in expression of FN and the ␣5␤1-integrin receptor in the AA of 1-year-old SHRs and Wistar rats. We discovered that SHRs and Wistar rats expressed equivalent elastic properties of the wall material…”

mentioning

confidence: 99%

Fibronectin Expression and Aortic Wall Elastic Modulus in Spontaneously Hypertensive Rats

Bézie

Lamazière

Laurent

et al. 1998

ATVB

146

153

View full text Add to dashboard Cite

Abstract-Recent studies have shown that large-artery wall remodeling per se does not reduce distensibility in hypertension, indicating qualitative or quantitative changes in arterial components. The aim of the study was to determine in 1-year-old spontaneously hypertensive rats (SHRs) the changes in the elastic properties of large arteries, as assessed by the incremental elastic modulus (E inc ), and the changes in the extracellular matrix, including fibronectin (FN) and ␣5␤1-integrin. The relationship between E inc and circumferential wall stress was calculated from in vivo pulsatile changes in blood pressure and arterial diameter by using a high-resolution echo-tracking system at the site of the abdominal aorta and in vitro medial cross-sectional area. E inc -stress curves and FN and integrin ␣5-subunit contents were determined for each animal. Mean stress and E inc were higher in SHRs than in Wistar rats. However, in a common range of stress, E inc -stress curves for SHRs were superimposable on those for Wistar rats, indicating that wall materials in both strains have equivalent mechanical behavior. Immunohistochemistry indicated that total FN, EIIIA FN isoform, and ␣5-integrin increased in the SHRs aortas without changes in elastin and collagen densities. Key Words: SHR Ⅲ elastic modulus Ⅲ aorta Ⅲ fibronectin Ⅲ ␣5␤1-integrin T he mechanical properties of large arteries play a major role in cardiovascular hemodynamics through the buffering of stroke volume and the propagation of the pressure pulse.1,2 It is well recognized that mechanical properties of large arteries are primarily determined by the composition of the arterial wall. The ECM proteins, mainly collagen and elastin, influence the "passive" mechanical properties of the arterial wall whereas its "active" properties depend on the activation of VSMCs.It was generally accepted that hypertension produced an increase in large-artery stiffness.1-4 However, recent studies have shown that arterial stiffness is not increased, despite wall hypertrophy, in either hypertensive patients or SHRs. [5][6][7][8][9] This finding suggests that sustained hypertension is associated with a rearrangement of the arterial wall material, implying qualitative or quantitative changes in arterial components leading to the mechanical adaptation of the arterial wall.The elastic properties of the arterial wall material depend not only on the SMC, elastin, and collagen contents but also on the way these components are spatially organized within the media. 3,10,11 Through an interaction with specific cellular integrin receptors, FN plays an important role in cell-matrix interactions. In addition, FN may also influence VSMC phenotype.12-14 The present study was undertaken to relate the changes in the elastic properties of the arterial wall material to its composition in the ECM and to focus on FN and its specific receptor, the ␣5␤1-integrin.The interaction of specific ECM proteins with their integrin receptors has been shown to play a central role in transmitting mechanical forces to...

show abstract

“…79,80 Furthermore, hypertension in different rat animal models has been shown to rapidly increase ED-A-positive FN expression (3-to 6-fold), correlating with the degree of blood pressure elevation; this expression is reversed by normalization of the blood pressure. [81][82][83] Similar to FN expression in atherosclerosis, angiotensin II rapidly increases FN expression in the aortic wall after a 3-day infusion, an effect that is inhibited by angiotensin II receptor blockade and occurs independently of the increase in blood pressure. 84 The end-organ damage seen in the heart in hypertension is characterized by a marked increase in FN expression.…”

Section: Fn and Hypertensionmentioning

confidence: 99%

Fibronectin

Magnússon

Mosher

1998

ATVB

263

View full text Add to dashboard Cite

In the past 2 decades, it has been appreciated that the functions of the extracellular matrix (ECM) are not entirely structural. ECM components interact with specific adhesion receptors on cell surfaces and regulate various cellular functions, including differentiation, proliferation, migration, and apoptosis. Fibronectin (FN) is a paradigm adhesive protein, nonreactive with adhesion receptors in its soluble state but highly adhesive when insoluble. Polymerization of FN into the ECM must be tightly regulated to ensure that the adhesive information in the ECM is appropriate.FN exists in a soluble protomeric form in micromolar concentration in blood plasma and in an insoluble multimeric form in the ECM.1,2 Unlike fibrillar or basement membrane collagens, laminins, actin, and tubulin, circulating FN does not self-polymerize in physiologically relevant solutions. Furthermore, there is little passive accumulation of FN in preexisting ECM. Rather, assembly of FN takes place at specialized areas on the cell surface.3 FN is especially abundant in the ECM of embryonic and regenerating or injured tissues, although it can be found in most ECMs, including basement membranes. FN interacts with cells through integrins, heterodimeric transmembrane receptors linking the ECM to the intracellular cytoskeleton and signaling pathways. The aim of this review is to describe the mechanisms and consequences of FN deposition and give a brief overview of the significance of FN for selected areas of cardiovascular research. In the first section we describe important features of the FN molecule that account for its multiple functions. Next, we focus on the assembly process, ie, the conversion of soluble FN to its active, adhesive, insoluble form. Finally, we discuss several areas of cardiovascular research in which FN may have an important role, exemplifying how the adhesive information of FN can drive pathophysiological processes. Structure of FNSoluble FN is a dimeric glycoprotein. Each subunit is a mosaic of a series of repeating modules: 12 type I modules, 2 type II, 15 to 17 (depending on splicing) type III, and a variable (V) sequence that is not homologous to other parts of FN (Figure 1). The deduced amino acid sequences for FNs of the clawed frog and rat are well conserved, possessing 71% amino acid identity and the same overall organization. 4 The 2 type III modules that are subject to alternative splicing are called ED-A (ED for "extradomain") and ED-B. Plasma FN is synthesized in the liver by hepatocytes and contains neither ED-A nor ED-B, whereas so-called "cellular" FN (synthesized locally in tissues) contains variable amounts of either or both ED-A and ED-B. 1,2 Furthermore, in plasma FN dimers, only 1 of the subunits contains the V region, whereas almost all cellular FN subunits contain this region. 5 FN binds to ␣ 5 ␤ 1 and ␣ IIb ␤ 3 integrins through a cell adhesive site comprising modules III8-III10. The most critical site is the Arg-Gly-Asp (RGD) sequence in III10. RGD peptides block integrin-mediated cell adhesion to FN...

show abstract

Fibronectin biosynthesis in the rat aorta in vitro. Changes due to experimental hypertension.

Cited by 37 publications

References 39 publications

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

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

Fibronectin Expression and Aortic Wall Elastic Modulus in Spontaneously Hypertensive Rats

Fibronectin

Contact Info

Product

Resources

About