Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload.

Itô, Haruo; Hiroe, Michiaki; Hirata, Yukio; Fujisaki, Hiroyuki; Adachi, Susumu; Akimoto, Hideaki; Ohta, Yoshiko; Marumo, Fumiaki

doi:10.1161/01.cir.89.5.2198

Cited by 219 publications

(109 citation statements)

References 23 publications

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“…Endothelin‐1 is increased systemically in HF (Ito et al. 1994; Lehmann et al. 2014) and we previously showed that coronary vessels from EC‐MR −/− have attenuated endothelin‐induced vasoconstriction (Mueller et al.…”

Section: Resultsmentioning

confidence: 99%

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

et al. 2017

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Heart Failure (HF) is associated with increased circulating levels of aldosterone and systemic inflammation. Mineralocorticoid receptor (MR) antagonists block aldosterone action and decrease mortality in patients with congestive HF. However, the molecular mechanisms underlying the therapeutic benefits of MR antagonists remain unclear. MR is expressed in all cell types in the heart, including the endothelial cells (EC), in which aldosterone induces the expression of intercellular adhesion molecule 1 (ICAM‐1). Recently, we reported that ICAM‐1 regulates cardiac inflammation and cardiac function in mice subjected to transverse aortic constriction (TAC). Whether MR specifically in endothelial cells (EC) contributes to the several mechanisms of pathological cardiac remodeling and cardiac dysfunction remains unclear. Basal cardiac function and LV dimensions were comparable in mice with MR selectively deleted from ECs (EC‐MR −/−) and wild‐type littermate controls (EC‐MR +/+). MR was specifically deleted in heart EC, and in EC‐containing tissues, but not in leukocytes of TAC EC‐MR −/− mice. While EC‐MR −/− TAC mice showed preserved systolic function and some alterations in the expression of fetal genes, the proinflammatory cytokine TNF α and the endothelin receptors in the LV as compared to EC‐MR +/+ TAC mice, no difference was observed between both TAC groups in overall cardiac hypertrophy, ICAM‐1 LV expression and leukocyte infiltration, cardiac fibrosis or capillary rarefaction, all hallmarks of pathological cardiac remodeling. Our data indicate that EC‐MR contributes to the transition of cardiac hypertrophy to systolic dysfunction independently of other maladaptive changes induced by LV pressure overload.

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Section: Resultsmentioning

confidence: 99%

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

et al. 2017

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“…We selected AII because it is an important vasoactive peptide and potent modulator of ET-1 production [20] and because important actions of AII are mediated, at least in part, through stimulation of ET-1 production [8,9]. Serum was selected because it is a complex, but physiologically relevant, stimulator of ET-1 production [22].…”

Section: Mrna Levelsmentioning

confidence: 99%

“…As a result of its vasoconstrictive and proliferative effects, ET-1 has been implicated in various pathogenic processes, including atherosclerosis, acute myocardial infarction and congestive heart failure [5][6][7]. It is thought that cardiac hypertrophy induced either by the important vasoactive peptide angiotensin II (AII), or by haemodynamic overload, may be mediated, at least in part, through ET-1 production and action [8,9]. Increased ET-1 transcription, translation and secretion from endothelial cells (EC) occurs in response to a variety of conditions, and is often rapid (reviewed in [3]).…”

Section: Introductionmentioning

confidence: 99%

Oestrogen and progesterone inhibit the stimulated production of endothelin-1

Morey

Razandi

Pedram

et al. 1998

Biochemical Journal

119

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Important vascular proteins such as endothelin-1 (ET-1) promote the development of cardiovascular diseases. Oestrogen, and perhaps progesterone, prevent the development of vascular disease in women through incompletely understood cellular mechanisms. We hypothesized that oestradiol or progesterone might regulate the production of ET-1 as a potential novel mechanism. We found that serum and angiotensin II (AII) significantly stimulated ET-1 secretion from cultured bovine aortic endothelial cells, inhibited 50-75 % by oestradiol or by progesterone. Serum and AII stimulated ET-1 mRNA levels, inhibited at least 70 % by oestradiol and by progesterone. Serum stimulated ET-1 transcription mainly through the first 43 nucleotides of the ET-1 promoter, but oestradiol and progesterone did

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“…1,2 However, after sustained external load, hearts can evolve to a state of decompensated hypertrophy resulting in cardiac dilation and loss of contractile function. Whereas it is known that overload-induced cardiac hypertrophy involves the participation of angiotensin II, 3 endothelin-1, 4 and fibroblast growth factor-2, 5 the molecular mechanisms responsible for the transition from compensated to decompensated hypertrophy are poorly defined.…”

mentioning

confidence: 99%

Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload

et al. 2006

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Abstract-Cardiac hypertrophy is associated with upregulation of vascular endothelial growth factor (VEGF) in the myocardium. Here, we evaluated the effects of a decoy VEGF receptor on heart morphology and function to a murine model of pressure overload hypertrophy. Mice were administered adenoviral vector encoding a decoy VEGF receptor (Ad-Flk), and their hearts were subjected to pressure overload by transverse aortic constriction (TAC). Treatment with Ad-Flk led to a net reduction in capillary density in hearts subjected to TAC. Ad-Flk also led to a reduction in TAC-induced cardiac hypertrophy and promoted left ventricle dilatation and a loss in contractile function. Treatment with Ad-Flk markedly increased myocardial fibrosis and collagen gene upregulation. In contrast, Ad-Flk had no effect on any of these parameters in sham-treated mice. Administration of a VEGF trap reagent diminished pressure overload cardiac hypertrophy and promoted the progression to heart failure but had no effect on sham-treated animals. These findings suggest that VEGF is required to maintain myocardial capillary density and that reductions in the vascular bed are associated with the transition from compensatory hypertrophy to failure. (Hypertension. 2006;47:887-893.)

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Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload.

Abstract: These data suggest that endogenous ET-1 synthesized in the cardiovascular system plays a role in the mechanism of cardiac hypertrophy during the early phase of pressure overload in vivo.

Cited by 219 publications

References 23 publications

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

Oestrogen and progesterone inhibit the stimulated production of endothelin-1

Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload

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