Myostatin and insulin-like growth factor-1 in hypertensive heart disease

Fernández‐Solà, Joaquim; Borrisser-Pairó, Francesc; Antúnez, Emília; Tobías, Ester

doi:10.1097/hjh.0000000000000493

Cited by 15 publications

(10 citation statements)

References 51 publications

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“…The decreased transcription of Igf1 in ISIAH adrenals is in a good agreement with the observation that IGF1 expression may be significantly decreased in the presence of hypertension [23]. An increase in the IGF1 production was reported in rats undergoing the compensatory growth of the adrenal gland following the unilateral adrenalectomy [24].…”

Section: Discussionsupporting

confidence: 83%

Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

et al. 2016

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BackgroundThe adrenals are known as an important link in pathogenesis of arterial hypertensive disease. The study was directed to the adrenal transcriptome analysis in ISIAH rats with stress-sensitive arterial hypertension and predominant involvement in pathogenesis of the hypothalamic-pituitary-adrenal and sympathoadrenal systems.ResultsThe RNA-Seq approach was used to perform the comparative adrenal transcriptome profiling in hypertensive ISIAH and normotensive WAG rats. Multiple differentially expressed genes (DEGs) related to different biological processes and metabolic pathways were detected.The discussion of the results helped to prioritize the several DEGs as the promising candidates for further studies of the genetic background underlying the stress-sensitive hypertension development in the ISIAH rats. Two of these were transcription factor genes (Nr4a3 and Ppard), which may be related to the predominant activation of the sympathetic-adrenal medullary axis in ISIAH rats. The other genes are known as associated with hypertension and were defined in the current study as DEGs making the most significant contribution to the inter-strain differences. Four of them (Avpr1a, Hsd11b2, Agt, Ephx2) may provoke the hypertension development, and Mpo may contribute to insulin resistance and inflammation in the ISIAH rats.ConclusionsThe study strongly highlighted the complex nature of the pathogenesis of stress-sensitive hypertension. The data obtained may be useful for identifying the common molecular determinants in different animal models of arterial hypertension, which may be potentially used as therapeutic targets for pharmacological intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3354-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 83%

Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

et al. 2016

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“…Myocardial cell hypertrophy, as well as fibrosis, were evaluated by histological morphometry of each sample, as previously reported . Myocardial expression of FGF21 was measured by immunostaining with an anti‐FGF21 antibody (Abcam137715, 1/500, Abcam, Cambridge, UK).…”

Section: Methodsmentioning

confidence: 99%

Fibroblast growth factor‐21 protects against fibrosis in hypertensive heart disease

Ferrer-Curriu

Redondo-Angulo

Guitart‐Mampel

et al. 2019

The Journal of Pathology

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FGF21 is an endocrine factor that contributes to multiple pathophysiological processes, mainly via its action as a metabolic regulator and cardioprotective agent. Recent studies have shown increased circulating FGF21 levels in hypertensive patients and in mouse models of hypertension. However, the relevance of FGF21 in hypertensive heart disease has not been addressed. Hypertension was induced by treating 4‐month old WT and Fgf21−/− mice with angiotensin II (AngII) for 1 week, resulting in a similar increase in blood pressure in both genotypes. Plasma FGF21 levels and expression in heart and liver were significantly increased in hypertensive WT mice relative to controls, an effect that was associated with increased expression levels of β‐klotho specifically in the heart. Fgf21−/− mice developed a greater degree of hypertensive heart disease than WT mice, notably characterized by extensive cardiac dysfunction and fibrosis. In vitro and in vivo studies further showed that FGF21 exerted a marked protective effect against cardiac fibrosis. Finally, left ventricle biopsies from human hypertensive heart donors, especially those developing cardiomyopathy, showed a significant increase in FGF21expression compared with normotensive controls, a finding that was associated with significantly enhanced cardiac hypertrophy and fibrosis. We conclude that during hypertension, both systemic and cardiac‐produced FGF21 are induced and act on the heart, protecting it from hypertensive heart disease. Thus, FGF21 acts as key factor in the fibrogenesis associated with hypertensive heart disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…It has since then been found in other tissues in both mammalian and nonmammalian systems16. Mstn has been proposed as a putative new mediator of heart dysfunction, cardiac and extra-cardiac tissue fibrosis and cardiovascular cachexia1718192021.…”

mentioning

confidence: 99%

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

Verzola

Milanesi

Bertolotto

et al. 2017

Sci Rep

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Myostatin (Mstn) is a skeletal muscle growth inhibitor involved in metabolic disorders and heart fibrosis. In this study we sought to verify whether Mstn is also operative in atherosclerosis of abdominal aorta. In human specimens, Mstn expression was almost absent in normal vessels, became detectable in the media of non-progressive lesions and increased with the severity of the damage. In progressive atherosclerotic lesions, Mstn was present in the media, neointima, plaque shoulder and in infiltrating macrophages. Mstn co-localized with α-smooth muscle actin (α-SMA) staining and with some CD45+ cells, indicating Mstn expression in VSMCs and bloodstream-derived leukocytes. In vitro, Mstn was tested in VSMCs and monocytes. In A7r5 VSMCs, Mstn downregulated proliferation and Smoothelin mRNA, induced cytoskeletal rearrangement, increased migratory rate and MCP-1/CCR2 expression. In monocytes (THP-1 cells and human monocytes), Mstn acted as a chemoattractant and increased the MCP-1-dependent chemotaxis, F-actin, α-SMA, MCP-1 and CCR2 expression; in turn, MCP-1 increased Mstn mRNA. Mstn induced JNK phosphorylation both in VSMCs and monocytes. Our results indicate that Mstn is overexpressed in abdominal aortic wall deterioration, affects VSMCs and monocyte biology and sustains a chronic inflammatory milieu. These findings propose to consider Mstn as a new playmaker in atherosclerosis progression.

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Myostatin and insulin-like growth factor-1 in hypertensive heart disease

Abstract: The presence of hypertension significantly decreases IGF-1 myocardial expression. Myostatin myocardial expression increases in the presence of structural CMP either of hypertensive or other origin. These effects open the possibility of modulating hypertensive-induced cardiac damage.

Cited by 15 publications

References 51 publications

Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

Fibroblast growth factor‐21 protects against fibrosis in hypertensive heart disease

Myostatin mediates abdominal aortic atherosclerosis progression by inducing vascular smooth muscle cell dysfunction and monocyte recruitment

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