New insights into the roles of glucocorticoid signaling dysregulation in pathological cardiac hypertrophy

Yang, Jingmin; Chen, Yanying; Xiao, Li; Xu, Danyan

doi:10.1007/s10741-021-10158-x

Cited by 10 publications

(5 citation statements)

References 92 publications

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“…Pathological cardiac hypertrophy is a process of abnormal myocardium remodeling that initially occurs in response to numerous stimuli, such as ischemia and hypoxia, pressure or volume overload, hormones, etc., and eventually progresses to heart failure. It has emerged as an independent risk factor for increased morbidity and mortality of heart failure [17]. Currently, a variety of in vivo and in vitro experimental approaches to mimic cardiac hypertrophy have been developed to search for new therapeutic strategies, mainly including neurohormonal activation via inducers, such as ISO, angiotensin II, phenylephrine, and endothelin-1, as well as surgical procedures, for instance, transverse aortic constriction and coronary artery ligation [18].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Qiu,

Xie,

Ding

et al. 2024

Cureus

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Background and objectivesGinsenoside Re (Re), a protopanaxatriol-type saponin extracted from ginseng, is known to have potential cardioprotective effects; however, the mechanisms of Re in improving cardiac hypertrophy have not been fully elucidated. This study aimed to investigate the therapeutic effects and underlying mechanism of Re on isoproterenol (ISO)-induced cardiac hypertrophy in vivo and in vitro. MethodsRats were intraperitoneally injected with ISO 30 mg/kg thrice daily for 14 consecutive days to induce cardiac hypertrophy, and these rats were treated with atorvastatin (ATC, 20 mg/kg) or Re (20 mg/kg or 40 mg/kg) once daily for three days in advance until the end of the experiment. Heart weight index, hematoxylin and eosin staining, and hypertrophy-related fetal gene expression were measured to evaluate the effect of Re on cardiac hypertrophy in vivo. Meanwhile, the rat H9c2 cardiomyocyte hypertrophy model was induced by ISO 10 μM for 24 hours. Cell surface area and hypertrophy-related fetal gene expression were determined to assess the effect of Re on ISO-induced cardiomyocyte hypertrophy in vitro. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in both serum and cardiomyocytes were detected by enzymatic colorimetric assays. Furthermore, we chose cholesteryl ester transfer protein (CETP) as a target to explore the influence of Re on CETP expression in vivo and in vitro through real-time polymerase chain reaction, western blot, and enzymelinked immunosorbent assay. ResultsIntraperitoneal administration of ISO into rats resulted in increases in cross-sectional cardiomyocyte area, the ratio of heart weight to body weight, the ratio of left ventricular weight to body weight, and the ratio of right ventricular weight to body weight, as well as reactivation of fetal genes; however, treatment with Re or ATC ameliorated most of these hypertrophic responses. Similarly, Re pronouncedly alleviated ISO-induced cardiomyocyte hypertrophy, as evidenced by a decreased cell surface area and downregulation of fetal genes. Moreover, our in vivo and in vitro data revealed that Re reduced TC, TG, and LDL-C levels, and enhanced HDL-C levels. Re improved cardiac hypertrophy mainly associated with the inhibition of mRNA level and protein expression of CETP, to an extent comparable to that of the classical CETP inhibitor, anacetrapib. ConclusionsOur research found that CETP inhibition contributes to the protection of Re against ISO-induced cardiac hypertrophy, which provides evidence for the application of Re for cardiovascular disease treatments.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Qiu,

Xie,

Ding

et al. 2024

Cureus

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“…Glucocorticoids have long been known to impact cardiac biology [44][45][46]. Cardiomyocytes express high amounts of the glucocorticoid receptor and are responsive to cortisol signals in the body.…”

Section: Discussionmentioning

confidence: 99%

“…Cortisol, the principal glucocorticoid in humans plays an important role in maintaining the body's normal physiology, including the physiology of the heart. Overproduction of cortisol, brought on by stress or other factors, or treatment with high concentrations of synthetic glucocorticoids, can be deleterious to cardiac function-for example, it can provoke cardiac hypertrophy [46,50]. In culture, DEX treatment of embryonic or neonatal cardiomyocytes can likewise provoke a hypertrophic response [44,45], although those studies used a ten-fold higher concentration of this reagent than what we characterized as an optimal dose for supporting the long-term maintenance of a cardiac phenotype in culture.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Treatment Preserves the Structure of Adult Cardiac Explants and Supports Their Long-Term Contractility In Vitro

Eisenberg,

Kaur,

Castillo

et al. 2023

IJTM

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Normal contractile function of the myocardium is essential for optimal cardiovascular health. Evaluating drug effects on cardiomyocyte function at the cellular level is difficult for long-term studies. Present culture systems rely on isolated, cardiomyocyte preparations or cardiomyocytes derived from pluripotent stem cells (PSCs), all of which have limitations. Isolated, endogenous cardiomyocytes do not remain contractile in culture long term. While PSC-derived cardiomyocytes show contractile activity for longer periods of time, their phenotype is more embryonic than adult. Here we report that dexamethasone (DEX) treatment of adult mouse atrial tissue can extend its functionality in culture. Normally, cardiac explants cease their capacity as a contractile tissue within the first month, as the tissue flattens and spreads out on the culture substrate, while the cells dedifferentiate and lose their myocardial phenotype. However, with DEX treatment, cardiac explants maintain their contractile function, 3D morphology, and myocyte phenotype for up to 6 months. Moreover, DEX also preserved the contractile phenotype of isolated rat cardiomyocytes. These data with DEX suggest that simple modifications in culture conditions can greatly improve the long-term utility of in vitro model systems for screening drugs and agents that could be employed to alleviate human cardiac disease.

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“…GC has been associated with inducing cardiac hypertrophy via complex transcriptional activation and physiologic effects and with a notable sex bias for male subjects for such effects [ 15 ]. In neonates, septal and ventricular hypertrophy secondary to GC is usually benign and spontaneously resolves two to five weeks after GC is discontinued, though it did resolve earlier in our case [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Transient Global Ventricular Hypertrophy in a Patient With Multisystem Inflammatory Syndrome in Children (MIS-C) Correlated With High-Dose Glucocorticoid Treatment: A Case Report

West¹,

Dove²,

Kochilas³

et al. 2022

Cureus

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Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection has been shown to lead to depressed cardiac function. Standard treatment includes high-dose glucocorticoids (GC). We present the unusual case of a teenager who developed transient echocardiographic global ventricular hypertrophy following GC administration during his treatment for MIS-C, with the resolution of the hypertrophy after cessation of GC.

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New insights into the roles of glucocorticoid signaling dysregulation in pathological cardiac hypertrophy

Cited by 10 publications

References 92 publications

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy

Dexamethasone Treatment Preserves the Structure of Adult Cardiac Explants and Supports Their Long-Term Contractility In Vitro

Transient Global Ventricular Hypertrophy in a Patient With Multisystem Inflammatory Syndrome in Children (MIS-C) Correlated With High-Dose Glucocorticoid Treatment: A Case Report

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