Growth factor expression in aorta of normotensive and hypertensive rats.

Abstract

Hypertension causes biochemical and morphological changes in the vessel wall by unknown mechanisms. Locally produced substances may have a role in mediating these vascular changes. We have studied the expression of platelet-derived growth factor (PDGF) B chain and PDGF A chain, insulin-like growth factor (IGF)-I and IGF-II, endothelial cell growth factor (ECGF), basic fibroblast growth factor (bFGF), and transforming growth factor-, (TGF-ft) in aortic tissue from normotensive rats and rats made hypertensive by deoxycorticosterone (DOC)/salt treatment. Using Northern blotting, we found that genes for each of these growth factors were transcriptionally active in the aorta of both normotensive and hypertensive rats. TGF-ft aortic mRNA levels increased up to threefold as a result of DOC/salt hypertension. In contrast, no major changes in the expression of either PDGF chain, IGF-I

TGF-β 1 DNA Polymorphisms, Protein Levels, and Blood Pressure

“…Steady-state levels of TGF-␤ 1 mRNA are increased in the aorta of deoxycorticosterone-salt-sensitive hypertensive rats compared with normotensive rats. 4 Moreover, TGF-␤ 1 induces vascular smooth muscle cell hypertrophy in spontaneously hypertensive rats, which is not observed in normotensive WKY rats. 15 These observations, as well as the finding that direct transfer of TGF-␤ 1 gene into arteries results in fibrocellular hyperplasia suggest that TGF-␤ 1 plays a significant role in vascular remodeling in hypertensive conditions.…”

“…1 It is secreted by several cell types, including peripheral blood mononuclear cells, endothelial cells, and vascular smooth muscle cells, and induces fibrosis in a variety of tissues, including kidney, heart, and blood vessels. 2 Overproduction of TGF-␤ 1 , perhaps in part mediated by angiotensin II, has been linked to the sequela of chronic hypertension, including left ventricular hypertrophy, 3 vascular remodeling, 4 and progressive renal disease. 5 Although many of the biological actions of TGF-␤ 1 are mediated in an autocrine or paracrine fashion, data from transgenic mice have demonstrated that high circulating levels can mediate renal fibrosis and loss of function.…”

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

“…TGF-␤ 1 overexpression has been observed in the aorta of deoxycorticosteronesalt-sensitive, hypertensive rats (12,41), and cardiac myocytes, subjected to the hypertrophic stimulus of abdominal aortic constriction or norepinephrine infusion, display TGF-␤ 1 hyperexpression (42). On the other hand, prevention of myocardial hypertrophy with angiotensin-converting enzyme inhibitors is associated with decreased TGF-␤ 1 expression (43).…”

“…Overproduction, on the other hand, is an important mechanism for fibrogenesis (9,10). TGF-␤ 1 has been implicated in several of the long-term chronic sequelae of poorly controlled hypertension, including left ventricular hypertrophy (11), hypertensive vascular remodeling (12), and ESRD (13). Angiotensin II is a known stimulus of TGF-␤ 1 production; thus, TGF-␤ 1 may be an important mediator of angiotensin II-induced hypertensive damage (14).…”

Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195

“…Transforming growth factor-b has been implicated in vascular remodelling that accompanies hypertension [30] and in the pathogenesis of diabetic nephropathy [31]. Hyperglycaemia and AGEs increase TGFb production [22] and TGF-b stimulates the synthesis of individual matrix components such as collagens, fibronectin, laminin and proteoglycans [32,33] and simultaneously blocks matrix degradation by decreasing the synthesis of proteases and increasing concentrations of protease inhibitors [34,35].…”