Neuregulin-1 compensates for endothelial nitric oxide synthase deficiency

Shakeri, Hadis; Boen, Jente R A; Moudt, Sofie De; Hendrickx, Jhana O.; Leloup, Arthur; Jacobs, Griet; Meyer, Guido; Keulenaer, Gilles W. De; Guns, Pieter-Jan; Segers, Vincent F.M.

doi:10.1152/ajpheart.00914.2020

Cited by 15 publications

(5 citation statements)

References 71 publications

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“…Consonantly, previous studies also demonstrated the protective effects of NRG-1β in a mouse model of type 1 diabetes mellitus and Ang II–induced cardiorenal dysfunction, respectively. 36 , 37 …”

Section: Discussionmentioning

confidence: 99%

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats

Sárközy,

Watzinger,

Kovács

et al. 2023

JACC: Basic to Translational Science

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Section: Discussionmentioning

confidence: 99%

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats

Sárközy,

Watzinger,

Kovács

et al. 2023

JACC: Basic to Translational Science

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“…These studies indicate variant regulation of insulin- and ACh-mediated vasorelaxant responses. Additionally, neuregulin-1, a cardioprotective growth factor, was also shown to compensate for impaired NO production in the aorta of eNOS knockout mice ( Shakeri et al, 2021 ), again demonstrating that alternative pathways may compensate for endothelial NO dysfunction.…”

Section: Discussionmentioning

confidence: 96%

Aortic Stiffness in L-NAME Treated C57Bl/6 Mice Displays a Shift From Early Endothelial Dysfunction to Late-Term Vascular Smooth Muscle Cell Dysfunction

Moudt

Hendrickx²,

Neutel³

et al. 2022

Front. Physiol.

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Introduction and Aims: Endothelial dysfunction is recognized as a cardiovascular aging hallmark. Administration of nitric oxide synthase blocker N-Ω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) constitutes a well-known small animal model of cardiovascular aging. Despite extensive phenotypic characterization, the exact aortic function changes in L-NAME treated mice are largely unknown. Therefore, this study presents a longitudinal characterization of the aortic reactivity and biomechanical alterations in L-NAME treated C57Bl/6 mice.Methods and Results: Male C57Bl/6 mice were treated with L-NAME (0.5 mg/ml drinking water) for 1, 2, 4, 8, or 16 weeks. Peripheral blood pressure measurement (tail-cuff) and transthoracic echocardiograms were recorded, showing progressive hypertension after 4 weeks of treatment and progressive cardiac hypertrophy after 8–16 weeks of treatment. Aortic stiffness was measured in vivo as aortic pulse wave velocity (aPWV, ultrasound) and ex vivo as Peterson modulus (Ep). Aortic reactivity and biomechanics were investigated ex vivo in thoracic aortic rings, mounted isometrically or dynamically-stretched in organ bath set-ups. Aortic stiffening was heightened in L-NAME treated mice after all treatment durations, thereby preceding the development of hypertension and cardiac aging. L-NAME treatment doubled the rate of arterial stiffening compared to control mice, and displayed an attenuation of the elevated aortic stiffness at high distending pressure, possibly due to late-term reduction of medial collagen types I, III, and IV content. Remarkably, endothelial dysfunction, measured by acetylcholine concentration-response stimulation in precontracted aortic rings, was only observed after short-term (1–4 weeks) treatment, followed by restoration of endothelial function which coincided with increased phosphorylation of endothelial nitric oxide synthase (S1177). In the late-disease phase (8–16 weeks), vascular smooth muscle cell (VSMC) dysfunction developed, including increased contribution of voltage-dependent calcium channels (assessed by inhibition with diltiazem), basal VSMC cytoplasmic calcium loading (assessed by removal of extracellular calcium), and heightened intracellular contractile calcium handling (assessed by measurement of sarcoplasmic reticulum-mediated transient contractions).Conclusion: Arterial stiffness precedes peripheral hypertension and cardiac hypertrophy in chronic L-NAME treated male C57Bl/6 mice. The underlying aortic disease mechanisms underwent a distinct shift from early endothelial dysfunction to late-term VSMC dysfunction, with continued disease progression.

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“…Согласно данным H. Shakeri и соавт. [60], введение NRG-1 предотвращает гипертрофию, фиброз сердца и почек, вызываемый дефицитом эндотелиальной синтазы оксида азота (eNOS); экспрессия NRG-1 регулируется микроРНК-134.…”

Section: нейрегулин-1 при гипертрофии и фиброзе миокардаunclassified

Diagnostic and therapeutic aspects of neuregulin-1: A review

et al. 2023

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In recent decades, the prospect of using a biomarker strategy for early personalized diagnosis of cardiovascular pathology has been actively explored. The use of new markers seems promising, and the search for an ideal marker is actively ongoing, which will make it possible to understand many mechanisms of cardiovascular diseases. In recent years, the attention of scientists has been actively focused on studying the role of neuregulin-1 as a laboratory biological marker in cardiac pathology. Neuregulins belong to a superfamily of epidermal growth factors that are synthesized by the vascular endothelium in response to ischemia, adrenergic stimulation, and oxidative stress. A number of studies have shown the potentially important diagnostic and prognostic value of assessing neuregulin-1 as a biological marker. It is expected that further scientific and clinical studies will demonstrate the possibility of using this marker as an additional laboratory tool for diagnosing, risk stratifying and predicting cardiovascular events in patients with cardiovascular pathology. The therapeutic effect of recombinant neuregulin-1 on reducing morbidity and mortality in cardiac patients remains to be assessed in more detail.

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Neuregulin-1 compensates for endothelial nitric oxide synthase deficiency

Cited by 15 publications

References 71 publications

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats

Aortic Stiffness in L-NAME Treated C57Bl/6 Mice Displays a Shift From Early Endothelial Dysfunction to Late-Term Vascular Smooth Muscle Cell Dysfunction

Diagnostic and therapeutic aspects of neuregulin-1: A review

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