Neuregulin in Cardiac Hypertrophy in Rats With Aortic Stenosis

Rohrbach, Susanne; Yan, Xinhua; Weinberg, Ellen O.; Hasan, Faisal; Bartúnek, Jozef; Marchionni, Mark A.; Lorell, Beverly H.

doi:10.1161/01.cir.100.4.407

Cited by 122 publications

(49 citation statements)

References 40 publications

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“…All 4 are expressed in the heart, with ErbB1, ErB2 and ErbB4 declining with postnatal development (Camprecios et al, 2011). Although earlier studies documented expression of ErbB1, ErbB2 and ErbB4 only in adult heart (Sundaresan et al, 1998;Zhao et al, 1998;Rohrbach et al, 1999), more recent work also confirms adult expression of ErbB3 (Lorita et al, 2009;Camprecios et al, 2011).…”

Section: The Egfr Familymentioning

confidence: 98%

“…Cardiac ErbB2 and ErbB4 mRNA and protein levels increase with ventricular pressure overload during compensatory cardiac hypertrophy in mouse models, yet decline on transition to heart failure (Rohrbach et al, 1999). Subsequent work from these investigators showed reduced ErbB2 and ErbB4 expression and activity in patients with advanced heart failure (Rohrbach et al, 2005).…”

Section: Hypertrophy/heart Failurementioning

confidence: 99%

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Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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Section: The Egfr Familymentioning

confidence: 98%

Section: Hypertrophy/heart Failurementioning

confidence: 99%

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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“…The negative inotropic actions of NRG-1 may also explain why the myocardium downregulates ErbB2 and ErbB4 at the onset of heart failure 13 in an attempt to augment contractile performance. NOS inhibition attenuated the effects of NRG-1 on myocardial contractility, whereas inhibition of the prostaglandin pathway had no effect.…”

Section: Lemmens Et Almentioning

confidence: 99%

Neuregulin-1 Induces a Negative Inotropic Effect in Cardiac Muscle

et al. 2004

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Background-Deficient cardiac neuregulin/ErbB signaling increases susceptibility to heart failure. In this study, we examined the effects of neuregulin-1 (NRG-1) on myocardial contractility. Methods and Results-NRG-1 (␣ and ␤ isoforms) induced a negative inotropic effect in isolated rabbit papillary muscles and a rightward shift of the dose-response curve to isoproterenol. Both effects were attenuated by L-NMMA, which suggests a role for NO synthase. In cultured rat cardiomyocytes, NRG-1␤ enhanced nitrite production and resulted in phosphorylation of endothelial NO synthase and the serine/threonine kinase Akt. Conclusions-NRG-1 has negative inotropic effects that are preserved during ␤-adrenergic stimulation and activates endothelial NO synthase in cardiomyocytes. Key Words: neuregulin Ⅲ nitric oxide synthase Ⅲ endothelium Ⅲ contractility Ⅲ heart failure M onoclonal antibodies against the neuregulin (NRG) receptor ErbB2 (Trastuzumab), used in the treatment of breast cancer, may induce dilated cardiomyopathy and heart failure. 1 From this observation, it was hypothesized that the NRG/ErbB pathway may participate in the pathogenesis of heart failure.In the fetal heart, NRG-1 has been detected in endothelial cells, whereas ErbB2 and ErbB4 receptors are expressed throughout the myocardium. Targeted mutagenesis of NRG-1, ErbB2, or ErbB4 results in embryonic lethality due to failure of myocardial trabeculation. 2,3 The ErbB3 receptor is present in endocardial cushion mesenchyme, and ErbB3-deficient mice exhibit cardiac cushion abnormalities. 4 In the adult heart, ErbB2 and ErbB4 are found in the T-tubule system of cardiomyocytes, whereas NRG-1 is expressed in endocardial and microvascular endothelial cells. 2 Conditional mutation of cardiac ErbB2 leads to dilated cardiomyopathy, which suggests a role for the NRG/ ErbB pathway in heart failure. 5 Experimental studies have shown that NRG-1 promotes survival and hypertrophic growth of adult cardiac myocytes in vitro. 2,6 In the present study, we characterized the direct effects of NRG-1 on contractility of adult cardiac muscle and the possible contribution of the Akt-NO synthase (NOS) pathway in these effects. Methods Mechanical PerformanceIsometric contractions were recorded from papillary muscles isolated from the right ventricle of New Zealand White rabbits with an electromagnetic length-force transducer as described previously. 7,8 After determination of the length at which peak twitch active tension is maximal (L max ), stabilized muscles were randomly assigned to one of the following treatment protocols: (1) muscles kept in baseline conditions (control group), (2) muscles in which NRG-1␣2 epidermal growth factor (EGF) domain (500 ng/mL or 71 nmol/L, Sigma; hereafter referred to as NRG-1␣) or NRG-1␤1 EGF domain (100 ng/mL or 13 nmol/L, Sigma; hereafter referred to as NRG-1␤) was added at time zero, or (3) muscles exposed to indomethacin (10 mol/L, Merck Sharp & Dohme), L-NMMA (N G -methyl-L-arginine, acetate salt, 50 mol/L, Sigma), or the tyrosine kinase inhibitor ge...

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“…9,15 The following antibodies were used to measure levels of LV proteins: antimuscarinic AChR-M 2 (Santa Cruz Biotechnology); anti-G protein subunits G␣ i1,2 , G␣ i3 , and G␣ o (Calbiochem); and anti-endothelial NO synthase (eNOS) and anti-inducible NO synthase (iNOS) (BD Biosciences). Protein levels of the nicotinic receptor AChR-␤ 1 (Santa Cruz Biotechnology) were investigated in brain lysates.…”

Section: Western Blottingmentioning

confidence: 99%

“…7,8 We demonstrated that left ventricular (LV) erbB2 and erbB4 protein levels are decreased in experimental heart failure 9 and that mice with conditional erbB2 mutation develop cardiomyopathy. 10,11 These data support the concept that neuregulin-erbB signaling is cardioprotective, but the responsible mechanisms are incompletely understood.…”

mentioning

confidence: 99%

Neuregulins Regulate Cardiac Parasympathetic Activity

et al. 2004

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Background-Neuregulins are required for maintenance of acetylcholine receptor-inducing activity of nicotinic receptors in neurons and skeletal muscle, but effects of neuregulins on muscarinic receptors are not known. In the normal heart, parasympathetic activation counterbalances ␤-adrenergic activation. To test the hypothesis that neuregulins modify parasympathetic function in the heart, we studied cardiomyocytes from mice heterozygous for neuregulin-1 gene deletion (NRG-1

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Neuregulin in Cardiac Hypertrophy in Rats With Aortic Stenosis

Cited by 122 publications

References 40 publications

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Neuregulin-1 Induces a Negative Inotropic Effect in Cardiac Muscle

Neuregulins Regulate Cardiac Parasympathetic Activity

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