Norepinephrine and ANG II stimulate secretion of TGF-beta by neonatal rat cardiac fibroblasts in vitro

Fisher, Stephen; Absher, Marlene

doi:10.1152/ajpcell.1995.268.4.c910

Cited by 88 publications

(47 citation statements)

References 23 publications

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“…28 In addition, Ang II directly stimulates the proliferation, as well as the production, of extracellular matrix proteins by cardiac fibroblasts, 29 and TGF-␤1 participates in the Ang II-induced synthesis of collagens by these cells. 30,31 In the present study, candesartan reduced both the extent of cardiac fibrosis and the amount of TGF-␤1 mRNA in the hearts of DS rats, suggesting that AT 1 receptor signaling through TGF-␤1 contributes to the development of fibrosis apparent in these animals. 25 These observations are also consistent with the results of experimental studies suggesting that Ang II induces cardiac fibrosis, not as a result of its hypertensive effect, but by a direct action on the heart.…”

Section: Discussionsupporting

confidence: 55%

AT ₁ Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats

et al. 2002

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Abstract-The possible role of calcineurin in the attenuation of cardiac hypertrophy and fibrosis by blockade of the angiotensin II type 1 (AT 1 ) receptor was investigated in Dahl salt-sensitive (DS) rats. The effect of the calcineurin inhibitor FK506 was also studied. DS rats progressively developed severe hypertension when fed a diet containing 8% NaCl from 7 weeks of age. In addition, marked cardiac hypertrophy and fibrosis were apparent and the activity of calcineurin and its mRNA expression in the myocardium was increased in these animals at 12 weeks in comparison with age-matched Dahl salt-resistant rats. The abundance of angiotensin-converting enzyme (ACE) and transforming growth factor (TGF)-␤1 mRNAs was also increased in the hearts of DS rats at 12 weeks. Treatment of DS rats with a non-antihypertensive dose of the selective AT 1 receptor blocker candesartan (1 mg/kg per day) or FK506 (0.1 mg/kg per day) from 7 to 12 weeks attenuated both calcineurin activity and its mRNA expression in the heart, as well as the development of cardiac hypertrophy and fibrosis, without affecting cardiac function. There are at least 2 isoforms for Ang II receptors, which are designated as AT 1 and AT 2 , and the AT 1 receptor is further subdivided into AT 1A and AT 1B . It is generally accepted that most of the traditional Ang II functions in the cardiovascular system are attributable to the AT 1 receptor. 3 Angiotensin-converting enzyme (ACE) inhibitors or AT 1 receptor blockers induce the regression or prevent the development of left ventricular (LV) hypertrophy, both in animal models 4 -6 and in hypertensive patients. 7,8 However, it has proved difficult to determine whether the antagonistic effects of ACE inhibitors and AT 1 receptor blockers on Ang II-induced growth promotion or the concomitant systemic hemodynamic effects of these agents underlie their beneficial action with regard to this condition. A non-antihypertensive dose of an ACE inhibitor was shown to reverse LV hypertrophy in aortic banded rats, 9,10 and the antihypertrophic effect of an AT 1 receptor blocker was shown to be greater than that of hydralazine, despite the greater antihypertensive effect of hydralazine, in spontaneously hypertensive rats. 6 These observations suggest that blood pressure reduction alone is not sufficient to prevent target organ damage and that the additional control of local or neurohumoral factors might also be required.An intracellular signaling pathway that includes the Ca 2ϩ -dependent protein phosphatase calcineurin has been shown to underlie cardiac hypertrophy. 11 Calcineurin has also been shown to play a key role in the development of pressure overload-induced cardiac hypertrophy. 12,13 A recent study suggested that calcineurin is involved in the development of cardiac hypertrophy induced by mineralocorticoid excess. 14 Furthermore, treatment of cultured cardiac myocytes with Ang II or phenylephrine results in activation of calcineurin. 15 However, the effect of the cardiac renin-angiotensin system (RAS) on calcineurin ...

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Section: Discussionsupporting

confidence: 55%

AT ₁ Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats

et al. 2002

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“…This is based on several in vitro findings. Thus, cardiac fibroblasts express AT1 receptors (16,17), and Ang II induces mitogenic responses (18,19), and increases protein synthesis (19), production of collagen (15,17), and TGF-β (20)(21)(22) in cardiac fibroblasts. These studies support the notion that Ang II can directly act on cardiac fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice

Matsusaka¹,

Katori²,

Inagami³

et al. 1999

J. Clin. Invest.

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“…Indeed, cardiac fibroblasts are the principal cellular origin of TGF-β 1 and in cultured rat adult cardiac fibroblasts ANG II stimulates TGF-β 1 gene expression, increases total TGF-β 1 production and promotes the conversion of latent TGF-β 1 to the active form [50,[55][56][57][58][59]. Simultaneous treatment of cardiac fibroblasts in vitro with ANG II and a neutralizing antibody to TGF-β 1 reduces type I and type III collagen mRNA expression [59] and collagen production ( Fig.…”

Section: Ang Ii-induced Collagen Production and Degradation During Inmentioning

confidence: 98%

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

Lijnen¹

2011

TOHYPERJ

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Angiotensin II increases the NAD(P)H-dependent superoxide anion production and the intracellular generation of reactive oxygen species in cardiac fibroblasts and apocynin, a NAD(P)H oxidase inhibitor, abrogates this rise. The membrane associated NAD(P)H oxidase complex is the predominant source of superoxide anion and reactive oxygen species generation in angiotensin II-stimulated adult cardiac fibroblasts. Inhibition of this NAD(P)H oxidase complex with apocynin completely blocks the angiotensin II-stimulated collagen production, collagen I and III protein and mRNA expression.Superoxide anion production is also increased by the Cu,Zn-superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) and decreased by the superoxide scavenger tempol in control and ANG II-treated fibroblasts. ANG II and DETC stimulate the collagen production and the collagen I and fibronectin content in fibroblasts. The SOD mimetics tempol and EUK-8 as well as polyethyleneglycol-SOD reduce the collagen production.ANG II also decreases the activity and mRNA and protein expression of the mitochondrial antioxidants Mn-SOD and peroxiredoxin-3. Upon phosphorylation of Akt by ANG II, P-Akt is translocated from the cytoplasm to the nucleus and nuclear phosphorylation of FOXO3a by P-Akt leads to relocalisation of FOXO3a from the nucleus to the cytosol, resulting in a decrease in its transcriptional activity and in Mn-SOD expression. These data indicate that ANG II inactivates FOXO3a by activating Akt and this leads to a reduction in the expression of the antioxidant Mn-SOD. A role of SOD and the formed reactive oxygen species in the regulation and organization of collagen in cardiac fibroblasts is suggested.

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Norepinephrine and ANG II stimulate secretion of TGF-beta by neonatal rat cardiac fibroblasts in vitro

Cited by 88 publications

References 23 publications

AT ₁ Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats

AT ₁ Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats

Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

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Norepinephrine and ANG II stimulate secretion of TGF-beta by neonatal rat cardiac fibroblasts in vitro

Cited by 88 publications

References 23 publications

AT 1 Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats

AT 1 Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats

Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

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AT ₁ Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats

AT ₁ Receptor Blockade Reduces Cardiac Calcineurin Activity in Hypertensive Rats