The Effects of Endothelin-1 on Collagen Type I and Type III Synthesis in Cultured Porcine Coronary Artery Vascular Smooth Muscle Cells

Rizvi, Masood Ahmad

doi:10.1006/jmcc.1996.0023

Cited by 110 publications

(65 citation statements)

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“…20 Recent studies indicate that at least part of this pathological process is independent of changes in hemodynamics and could be attributed to the role of locally formed profibrogenic factors. 7,21 The purpose of the present study was to examine whether ET-1 is involved in the development of renal vascular fibrosis observed during NO deficiency. Several in vitro and in vivo studies suggest that ET-1 synthesis is activated during impairment of the NO pathway.…”

Section: Discussionmentioning

confidence: 99%

“…ET-1 has mitogenic properties and the ability to regulate extracellular matrix synthesis by vascular smooth muscle cells (VSMCs) in vitro. 7 Because collagen I is almost absent in renal vessels and glomeruli, it is considered to be a marker of pathophysiological process in abnormal vascular remodeling. 8 Therefore, we hypothesized that longterm blockade of vascular NO production would be associated with enhanced renal vascular production of both ET-1 and collagen I.…”

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confidence: 99%

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Vascular Endothelin-1 Gene Expression and Synthesis and Effect on Renal Type I Collagen Synthesis and Nephroangiosclerosis During Nitric Oxide Synthase Inhibition in Rats

et al. 1999

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Background-The progression of hypertension during NO deficiency is associated with renal vascular fibrosis due to increased extracellular matrix (mainly collagen I) formation. The purpose of the present study was to investigate whether endothelin-1 (ET-1) is involved in this pathophysiological process. Methods and Results-Treatment of rats for 4 weeks with the NO synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME) 50 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 increased systolic blood pressure to 159Ϯ12 mm Hg. In animals treated with L-NAME, histological evaluation of renal sections revealed an increased formation of extracellular matrix (Masson's trichrome), and specifically of collagens (Sirius red). A part of this fibrosis was attributed to abnormal collagen I presence, because mRNA expression of the collagen I ␣1 chain (reverse transcription-polymerase chain reaction) and procollagen I formation (radioimmunoassay) were increased 3-and 2.5-fold, respectively, in the renal resistance vessels of hypertensive animals. In subsequent experiments, we examined whether ET-1 was involved in activation of collagen I formation. mRNA expression (RNase protection assay) of preproET-1 and ET-1 content (radioimmunoassay) were 10-fold and 3-fold increased, respectively, in renal microvessels of rats treated with L-NAME. Interestingly, in these vessels, ET-1 (immunostaining) was colocalized with sudanophilic lesions. Bosentan, an ET receptor antagonist (20 mg, coadministered with L-NAME canceled the increased mRNA expression and synthesis of collagen I and attenuated the severity of renal vascular lesions without affecting L-NAME-induced high blood pressure. Conclusions-These data demonstrate that ET-1 synthesis is increased in renal microvessels when NO production is suppressed. In this model of hypertension, ET-1 is a major activator of collagen I formation in renal resistance vessels and participates in the development of renal fibrosis without affecting systolic blood pressure. (Circulation. 1999;99:2185-2191.)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Vascular Endothelin-1 Gene Expression and Synthesis and Effect on Renal Type I Collagen Synthesis and Nephroangiosclerosis During Nitric Oxide Synthase Inhibition in Rats

et al. 1999

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“…5 In vitro and/or pharmacological studies have suggested that ET-1 exerts trophic effects in cardiac myocytes 6 and stimulates collagen synthesis in fibroblasts. 7 ET-1 also modulates leukocyte adhesion to endothelial cells 8 and enhances production of cytokines in monocytes/macrophages. 9 However, the role of ET-1 in the pathogenesis of CHF remains controversial.…”

mentioning

confidence: 99%

Conditional Cardiac Overexpression of Endothelin-1 Induces Inflammation and Dilated Cardiomyopathy in Mice

Yang

Gros²,

Kabir³

et al. 2004

Circulation

155

113

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Background-Myocardial expression of endothelin-1 (ET-1) and its receptors ET A and ET B is increased in heart failure.However, the role of ET-1 and its signaling pathways in the pathogenesis of myocardial diseases is unclear. Methods and Results-Human ET-1 cDNA was placed downstream of a promoter responsive to a doxycycline (DOX)-regulated transcriptional activator (tTA). This line (ET ϩ ) was bred with one harboring cardiac myocyterestricted expression of tTA (␣MHC-tTA). Myocardial ET-1 peptide levels were significantly increased in binary transgenic (BT, ET ϩ /tTA ϩ ) compared with nonbinary transgenic (NBT, ET ϩ /tTA Ϫ ; ET Ϫ /tTA ϩ ; ET Ϫ /tTA Ϫ ) or DOX-treated BT littermates (40.1Ϯ4.7 versus 2.6Ϯ1.2 fmol/mL, PϽ0.003). BT mice demonstrated progressive mortality between 5 and 11 weeks after DOX withdrawal, associated with left ventricular dilatation and contractile dysfunction (peak ϩdP/dT, 4673Ϯ468 versus 5585Ϯ658 mm Hg/s, PϽ0.05). An interstitial inflammatory infiltrate, including macrophages and T lymphocytes, was evident in the myocardium of BT mice, associated with sequential increases in nuclear factor-B translocation and expression of tumor necrosis factor-␣, interferon-␥, interleukin-1 and interleukin-6. Significant prolongation of survival was observed with the combined ET A /ET B antagonist LU420627 (nϭ8, PϽ0.05) in BT mice but not the ET A -selective antagonist LU135252 (nϭ5, Pϭ0.9), consistent with an important role for ET B in this model. Conclusions-These are the first data to demonstrate that cardiac overexpression of ET-1 is sufficient to cause increased expression of inflammatory cytokines and an inflammatory cardiomyopathy leading to heart failure and death.

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“…The specific ET A receptor antagonist BQ123 significantly inhibited the stimulatory effects of ET-1 in an in vitro study. 37 Furthermore, clear evidence of reduced collagen deposition was observed in pig iliac arteries treated with ABT127722.5, the racemate of ABT147627. 18 Coronary balloon injury in the porcine model not only induces smooth muscle cell proliferation and collagen synthesis but also stimulates the proliferation and migration of adventitial myofibroblasts across the external elastic lamina toward the coronary lumen.…”

Section: Discussionmentioning

confidence: 97%

Selective ETA Receptor Antagonism Reduces Neointimal Hyperplasia in a Porcine Coronary Stent Model

McKenna¹

1998

Journal of the American College of Cardiology

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Background-As endothelin binds to ET A receptors, it stimulates vascular smooth muscle cell proliferation and may thus be pivotally involved in the pathogenesis of restenosis. This study assessed the ability of a potent and selective ET A antagonist to reduce neointimal hyperplasia in a porcine coronary artery stented injury model. Methods and Results-Fifty-five pigs were randomized to receive placebo or the oral ET A -selective antagonist ABT147627 twice daily for 28 days in one of three doses: 0.75 mg/kg (low), 3.75 mg/kg (mid), and 10.0 mg/kg (high). Each underwent oversized stent deployment in two randomly assigned major epicardial coronary arteries. Three animals (5.5%) died as a consequence of stent thrombosis within 24 hours of the procedure. The remaining 52 animals (13 pigs per group) survived without complication until predetermined euthanasia at 28 days. In the placebo group, mean injury score was 1.

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The Effects of Endothelin-1 on Collagen Type I and Type III Synthesis in Cultured Porcine Coronary Artery Vascular Smooth Muscle Cells

Cited by 110 publications

References 0 publications

Vascular Endothelin-1 Gene Expression and Synthesis and Effect on Renal Type I Collagen Synthesis and Nephroangiosclerosis During Nitric Oxide Synthase Inhibition in Rats

Vascular Endothelin-1 Gene Expression and Synthesis and Effect on Renal Type I Collagen Synthesis and Nephroangiosclerosis During Nitric Oxide Synthase Inhibition in Rats

Conditional Cardiac Overexpression of Endothelin-1 Induces Inflammation and Dilated Cardiomyopathy in Mice

Selective ETA Receptor Antagonism Reduces Neointimal Hyperplasia in a Porcine Coronary Stent Model

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