Angiotensin II and Endothelin-1 Increase Fibroblast Growth Factor-2 mRNA Expression in Vascular Smooth Muscle Cells

Peifley, Kimberly A.; Winkles, Jeffrey A.

doi:10.1006/bbrc.1997.7940

Cited by 66 publications

(29 citation statements)

References 32 publications

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“…1,2 ET-1 has vasoconstrictive and mitogenic effects, stimulates the production of growth factors such as vascular endothelial growth factor and basic fibroblast growth factor, and potentiates the effects of transforming growth factor-␤ and platelet-derived growth factor. [3][4][5][6][7] Chronic ET-1 stimulation can result in myocardial fibrosis and hypertrophy and vascular fibrosis with extracellular matrix proliferation. 8 In the lung, ET-1 is abundantly expressed in the pulmonary vasculature and appears to play an important role in the regulation of pulmonary vascular tone.…”

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confidence: 99%

Endothelin Receptor Blockers in Cardiovascular Disease

Rich¹,

McLaughlin²

2003

Circulation

199

126

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Abstract-The endothelin (ET) system is comprised of 4 active ETs, with ET-1 being the predominant isoform in the cardiovascular system. Because of the potent vasoconstricting and mitogenic effects of ET-1 and its involvement in various cardiovascular diseases, blockade of the ET receptor has received considerable attention. ET receptor antagonism has been demonstrated to be beneficial in patients with pulmonary hypertension. The nonselective ET receptor antagonist bosentan improves exercise capacity and increases time to clinical worsening in patients with pulmonary arterial hypertension. Key Words: endothelin Ⅲ heart failure Ⅲ pulmonary heart disease T he endothelin (ET) system, like other vascular regulatory systems, consists of a parent peptide that undergoes enzymatic activation and exerts its biologic effects by modulating specific receptors. Of the 4 active ETs (ET 1 through 4), ET-1 is the predominant isoform in the cardiovascular system, which is generated through the cleavage of prepro ET-1 to big ET-1 and then to ET-1 by the action of ET-converting enzymes. ET-1 is found in endothelial cells and is released toward the vascular smooth muscle consistent with a paracrine role, but it is also produced by smooth muscle cells and cardiomyocytes. 1,2 ET-1 has vasoconstrictive and mitogenic effects, stimulates the production of growth factors such as vascular endothelial growth factor and basic fibroblast growth factor, and potentiates the effects of transforming growth factor-␤ and platelet-derived growth factor. 3-7 Chronic ET-1 stimulation can result in myocardial fibrosis and hypertrophy and vascular fibrosis with extracellular matrix proliferation. 8 In the lung, ET-1 is abundantly expressed in the pulmonary vasculature and appears to play an important role in the regulation of pulmonary vascular tone. 9 ET-1 is also produced in leukocytes where it influences the production of a wide range of cytokines in the inflammatory response. 10 ET is regulated in an autocrine fashion by physiochemical factors such as blood flow, pulsatile stretch, sheer stress, and pH. 11-13 Acute hypoxia leads to selective stimulation of the ET-1 gene and ET synthesis in the pulmonary vasculature. 14 ET-1 biosynthesis is also stimulated by low-density lipoprotein cholesterol and glucose, and thrombin. 15,16 Endogenous inhibitors of ET-1 synthesis include nitric oxide, prostacyclin, atrial natriuretic peptides, and estrogens. [17][18][19][20] ET-1 exerts its major vascular effects through activation of 2 distinct G protein coupled ET A and ET B receptors. ET A receptors are found in the medial smooth muscle layers of the blood vessels, and atrial and ventricular myocardium. 21 When stimulated, the ET A receptors induce vasoconstriction and cellular proliferation by increasing intracellular calcium.ET B receptors are localized on endothelial cells and, to some extent, smooth muscle cells and macrophages. 22 The activation of ET B receptors stimulates the release of nitric oxide and prostacyclin and prevents apoptosis. 23 Normally, t...

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confidence: 99%

Endothelin Receptor Blockers in Cardiovascular Disease

Rich¹,

McLaughlin²

2003

Circulation

199

126

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“…In this pathological process, the universal underlying abnormality, which is mainly concerned with alterations in the structure and function of vascular smooth muscle cells (VSMCs), is enhanced by circulating and locally generated angiotensin (Ang) II, which affects the contractility and growth of VSMCs and the sympathetic nervous system. 6 Recent studies have reported that Ang II has pleiotropic effects on the proliferation of VSMCs, ie, the activation of mitogen-activated protein kinase 7 and the induction of growth factors 8 and proinflammatory cytokines. 9 In contrast, several investigators, although not all, have clinically shown that Ang II may contribute to glucose tolerance and the progression of diabetic cardiovascular and renal complications.…”

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confidence: 99%

Candesartan Inhibits Carotid Intimal Thickening and Ameliorates Insulin Resistance in Balloon-Injured Diabetic Rats

et al. 2001

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Abstract-This study investigates the effects of candesartan, an angiotensin II type 1 receptor blockade, on carotid arterial intimal thickening and glucose tolerance in balloon-injured male Wistar fatty rats and their littermates (Wistar lean rats). Candesartan was orally administered to 12-week-old rats for 21 days, and age-matched rats without the agent were used as the respective controls. Balloon catheterization in the left common carotid artery was performed on day 7, and the artery was removed on day 14 for histological analysis. Compared with the area ratios of the neointima/media in fatty rats without treatment, the ratios in fatty rats treated with candesartan at 1 mg · kg Ϫ1 · d Ϫ1 and lean rats without treatment were significantly decreased to 65%; on the other hand, the ratios of fatty rats treated with candesartan at 10 mg · kg Ϫ1 · dϪ1 and lean rats treated with 1 mg · kg Ϫ1 · d Ϫ1 were reduced to 35%, and those of lean rats treated with 10 mg · kg Ϫ1· d Ϫ1 were reduced to 28%. The administration of candesartan also decreased the level of plasma glucose time-and dose-dependently in fatty rats. In an intragastric glucose load, the levels of both glucose and insulin at 30 and 60 minutes were significantly decreased when fatty rats were treated with candesartan at 10 mg · kg Ϫ1 · d Ϫ1. In cultured vascular smooth muscle cells from fatty rats, insulin-stimulated Akt (New England Biolabs) phosphorylation and 2-deoxy-Dglucose uptake were inhibited to 59% and 68%, respectively, by angiotensin II, but the effects were ameliorated by the addition of 10 Ϫ7 mol/L candesartan. We conclude that candesartan could be effective for the suppression of vascular smooth muscle cell growth dose-dependently in Wistar fatty and lean rats. Furthermore, the agent could improve insulin resistance in Wistar fatty rats. Key Words: angiotensin II Ⅲ receptors, angiotensin II Ⅲ rats Ⅲ balloon injury Ⅲ insulin resistance M ultiple epidemiological and clinical studies have established that diabetes mellitus and hypertension are the most crucial risk factors in the pathogenesis of atherosclerosis, including cardiovascular disease and subsequent sudden death. 1-3 Considerable evidence supports the view that insulin resistance, its concomitant compensatory hyperinsulinemia, and the related glucose intolerance are associated with hypertension, 4,5 although the mechanisms of interaction still need to be completely clarified. Therefore, for the prevention of atherosclerosis and diabetic complications, it is necessary to identify the hypotensive agents that are beneficial for glucose metabolism.The renin-angiotensin system plays a key role in the pathogenesis of hypertension and atherosclerosis. In this pathological process, the universal underlying abnormality, which is mainly concerned with alterations in the structure and function of vascular smooth muscle cells (VSMCs), is enhanced by circulating and locally generated angiotensin (Ang) II, which affects the contractility and growth of VSMCs and the sympathetic nervous system. 6 Recen...

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“…It has therefore been postulated that GPCR agonists convey their mitogenic stimulus through the expression of endogenous growth factors. In support of this concept, AII, ET-1, and ␣-Thr have been reported to stimulate the expression of several growth factors, including PDGF-AA (8)(9)(10), basic FGF (11)(12)(13), heparin-binding epidermal growth factor (EGF)-like growth factor (14), transforming growth factor ␤ 1 (15), and insulin-like growth factor 1 (16). However, little direct evidence has been reported to implicate any of these factors as a major autocrine mediator of VSMC proliferation.…”

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confidence: 87%

Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin

Taylor

Cheng

Pawlowski

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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Vasoactive GTP-binding protein-coupled receptor agonists such as angiotensin II (AII), endothelin-1 (ET-1), and ␣-thrombin (␣-Thr) have been reported to indirectly stimulate vascular smooth muscle cell (VSMC) proliferation by regulating the expression of one or more autocrine growth factors. Using ion-exchange, gel-filtration, and reverse-phase chromatographic purification methods, we isolated a major mitogenic protein present in AII-stimulated rat aortic smooth muscle (RASM) cell conditioned medium. Twenty N-terminal amino acids of the purified peptide were identified, and they had 75% amino acid sequence identity with mouse epiregulin, an epidermal growth factor (EGF)-related growth factor. We cloned the cDNA for rat epiregulin to determine its pattern of expression in G-protein-coupled receptor agonist-stimulated cells and confirm its activity as a mitogen. After treatment of RASM cells with AII, ET-1, or ␣-Thr for 1 h, induction of two epiregulin transcripts was observed, including a 4.8-kb transcript and a novel transcript of approximately 1.2 kb. Recombinant rat epiregulin was strongly mitogenic for RASM cells, stimulating DNA synthesis to levels similar to those induced by serum or platelet-derived growth factor and approximately 3-fold above that observed with saturating concentrations of EGF. In addition, epiregulin caused rapid EGF receptor activation in RASM cells. However, relative levels of EGF receptor tyrosine phosphorylation stimulated by epiregulin were less than those induced by EGF or betacellulin. Taken together, these results indicate that epiregulin is a potent VSMC-secreted mitogen, induced in common by AII, ET-1, and ␣-Thr, that may contribute to VSMC proliferation and vascular remodeling stimulated by vasoactive agonists.

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Angiotensin II and Endothelin-1 Increase Fibroblast Growth Factor-2 mRNA Expression in Vascular Smooth Muscle Cells

Cited by 66 publications

References 32 publications

Endothelin Receptor Blockers in Cardiovascular Disease

Endothelin Receptor Blockers in Cardiovascular Disease

Candesartan Inhibits Carotid Intimal Thickening and Ameliorates Insulin Resistance in Balloon-Injured Diabetic Rats

Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin

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