Fibronectin Expression and Aortic Wall Elastic Modulus in Spontaneously Hypertensive Rats

Abstract

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...

Structural and Genetic Bases of Arterial Stiffness

“…18 -21 Similar findings were obtained with SHR and SHR-SP for analyses of the carotid artery and abdominal aorta in comparisons of hypertensive strains and WistarKyoto (WKY) rats. 22,23 Thus, hypertension-induced wall thickening is not associated with an increase in arterial stiffness in patients with essential hypertension and in rat models of hypertension.…”

Different biomechanical properties of medial and adventitial layers of thoracic aorta in Wistar-Kyoto and spontaneously hypertensive rats

“…Previous studies showed that mechanical characteristics of thoracic aorta were not changed in SHR compared with WKY [2,19] . A study with carotid showed that arterial distensibility was increased in 4, 8 16, 32-week-old SHR and stroke prone SHR (SHR-SP) compared with that in normotensive control animals for similar blood pressure levels, although there was an age-related decrease in arterial distensibility in rats of all groups that was more pronounced in the SHR-SP and SHR compared with that in WKY rats [20] .…”

“…In addition, vascular component remodeling may occur far before arterial stiffness alteration as shown in this and previous studies. In contrast, the increased distensibility may be caused by the compensation of arteries in response to elevating blood pressure in young objects [2,19] , and arterial stiffness increases significantly with age which will be more pronounced in hypertensive objectives than normotensive control.…”

“…The medial layer is composed of vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM), such as collagen and elastin. Functionally, ECM influences the passive mechanical properties of the arterial wall whereas VSMCs are related to its active properties [2] . Endothelial cells in intimal layer regulate vascular tone by releasing various relaxing or constricting factors [3,4] .…”

Hypertension Promotes Phosphorylation of Focal Adhesion Kinase and Proline-Rich Tyrosine Kinase 2 in Rats: Implication for the Pathogenesis of Hypertensive Vascular Disease

“…In the process of atherosclerosis, inflammatory cytokines and adhesion molecules play important roles to develop atheroma that consists of fibrous cap and lipid core (Fukumoto et al 1997;Ross 1999;Shimokawa 2000;Libby and Aikawa 2002;Fukumoto et al 2004). It has been demonstrated that chronic hypertension accelerates vascular smooth muscle cells (VSMC) hypertrophy and extracellular matrix accumulation, which are substantially involved in the development of vascular remodeling and atherosclerosis (Lee et al 1983;Schwartz et al 1986;Bezie et al 1998). Vascular remodeling induced by hypertension is mainly caused by two factors; increased mechanical stress and up-regulated humoral factors such as angiotensin II (Tamura et al 1998;Shimokawa 2002).…”