Dynamin-2 mediates heart failure by modulating Ca2+-dependent cardiomyocyte apoptosis

Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Angiotensin II (ANG II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis. Inasmuch as hexarelin has been reported to have protective effects in this process, we examined whether hexarelin can prevent cardiomyocytes from ANG II-induced cell death. Cultured cardiomyocytes from neonatal rats were stimulated with ANG II. Apoptosis was evaluated using fluorescence microscopy, TdT-mediated dUTP nick-end labeling (TUNEL) method, flow cytometry, DNA laddering, and analysis of cell viability by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). It was found that incubation with 0.1 μmol/l ANG II for 48 h increased cardiomyocyte apoptosis. Administration of 0.1 μmol/l hexarelin significantly decreased this ANG II-induced apoptosis and DNA fragmentation and increased myocyte viability. To further investigate the underlying mechanisms, caspase-3 activity assay and mRNA expression of Bax, Bcl-2, and growth hormone secretagogue receptor (GHS-R; the supposed hexarelin binding site) were examined. GHS-R mRNA was abundantly expressed in cardiomyocytes and was upregulated after administration of hexarelin. These results suggest that hexarelin abates cardiomyocytes from ANG II-induced apoptosis possibly via inhibiting the increased caspase-3 activity and Bax expression induced by ANG II and by increasing the expression of Bcl-2, which is depressed by ANG II. Whether the upregulated expression of GHS-R induced by hexarelin is associated with this antiapoptotic effect deserves further investigation.

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The role of cardiomyocyte apoptosis in mechanisms of ischemic myocardial remodeling

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2008-3-33-38 ◽

2008 ◽

Vol 7 (3) ◽

pp. 33-38

Author(s):

A. P. Khlapov ◽

Yu. Yu. Vechersky ◽

N. V. Ryazantseva ◽

V. V. Kalyuzhin ◽

L. R. Mustafina ◽

...

Keyword(s):

Heart Failure ◽

Left Ventricle ◽

Coronary Arteries ◽

High Volume ◽

Cardiomyocyte Apoptosis ◽

Atherosclerotic Disease ◽

Myocardial Remodeling ◽

Early Stages

Here the role of cardiomyocyte apoptosis in mechanisms of ischemic myocardial remodeling was investigated. The samples of left ventricle were obtained on 50 patients with the diagnosed atherosclerotic disease of coronary arteries and heart failure. Obtained data allow to approve about the maximal importance of cardiomyocyte apoptosis at an early stages of ischemic myocardial remodeling. The role of cardiomyocyte apoptosis was decreased at a high volume of left ventricle. The received results suggest about an importance of cardiomyocyte apoptosis as an marker of ischemic myocardial remodeling and heart failure.

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Effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure by regulating TGF-β1/Smad3 signaling pathway

Bioscience Reports ◽

10.1042/bsr20200566 ◽

2020 ◽

Vol 40 (5) ◽

Author(s):

Chun Xie ◽

Huaxin Qi ◽

Lei Huan ◽

Yan Yang

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Cardiomyocyte Apoptosis ◽

Luciferase Reporter ◽

Rat Cardiomyocytes ◽

Smad 3 ◽

Tgf Β1

Abstract Purpose: The present study set out to investigate the effect of miR-195-5p on cardiomyocyte apoptosis in rats with heart failure (HF) and its mechanism. Methods: HF rat model and hypoxia/reoxygenation (H/R) cardiomyocyte model were established. miR-195-5p expression and transforming growth factor-β1 (TGF-β1)/signal transduction protein (Smad)3 signaling pathway in HF rats and H/R cardiomyocytes were interfered. miR-195-5p expression was tested by Rt-PCR, TGF-β1/Smad3 signaling pathway related proteins were detected by Western Blot, apoptosis of HF rat cardiomyocytes was tested by TUNEL, and apoptosis of cardiomyocytes induced by H/R was checked by flow cytometry. Results: miR-195-5p was lowly expressed in myocardium of HF rats, while TGF-β1 and Smad3 proteins were high-expressed. Up-regulating miR-195-5p expression could obviously inhibit cardiomyocyte apoptosis of HF rats, improve their cardiac function, and inhibit activation of TGF-β1/Smad3 signaling pathway. Up-regulation of miR-195-5p expression or inhibition of TGF-β1/Smad3 signaling pathway could obviously inhibit H/R-induced cardiomyocyte apoptosis. Dual-luciferase reporter enzyme verified the targeted relationship between miR-195-5p and Smad3. Conclusion: miR-195-5p can inhibit cardiomyocyte apoptosis and improve cardiac function in HF rats by regulating TGF-β1/Smad3 signaling pathway, which may be a potential target for HF therapy.

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Contribution of non-cardiomyocyte apoptosis to cardiac remodelling that occurs in the transition from compensated hypertrophy to heart failure in spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs19980374 ◽

1999 ◽

Vol 97 (2) ◽

pp. 239 ◽

Cited By ~ 3

Author(s):

Shuntaro IKEDA ◽

Mareomi HAMADA ◽

Kunio HIWADA

Keyword(s):

Heart Failure ◽

Spontaneously Hypertensive Rats ◽

Cardiomyocyte Apoptosis ◽

Cardiac Remodelling ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

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Severity of regional myocardial dysfunction is not affected by cardiomyocyte apoptosis in non-ischemic heart failure

Pharmacological Research ◽

10.1016/j.phrs.2010.09.006 ◽

2011 ◽

Vol 63 (3) ◽

pp. 207-215 ◽

Cited By ~ 9

Author(s):

Tommaso Prescimone ◽

Vincenzo Lionetti ◽

Chiara Caselli ◽

Giovanni D Aquaro ◽

Manuela Cabiati ◽

...

Keyword(s):

Heart Failure ◽

Myocardial Dysfunction ◽

Cardiomyocyte Apoptosis ◽

Ischemic Heart ◽

Ischemic Heart Failure

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Human trophoblast-derived exosomes attenuate doxorubicin-induced cardiac injury by regulating miR-200b and downstream Zeb1

Journal of Nanobiotechnology ◽

10.1186/s12951-020-00733-z ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Jie Ni ◽

Yihai Liu ◽

Lina Kang ◽

Lian Wang ◽

Zhonglin Han ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Cardiac Fibrosis ◽

Cardiac Injury ◽

Cardiomyocyte Apoptosis ◽

Luciferase Reporter ◽

Human Trophoblast ◽

Trophoblast Stem

AbstractHuman trophoblast stem cells (TSCs) have been confirmed to play a cardioprotective role in heart failure. However, whether trophoblast stem cell-derived exosomes (TSC-Exos) can protect cardiomyocytes from doxorubicin (Dox)-induced injury remains unclear. In the present study, TSC-Exos were isolated from the supernatants of human trophoblasts using the ultracentrifugation method and characterized by transmission electron microscopy and western blotting. In vitro, primary cardiomyocytes were subjected to Dox and treated with TSC-Exos, miR-200b mimic or miR-200b inhibitor. Cellular apoptosis was observed by flow cytometry and immunoblotting. In vivo, mice were intraperitoneally injected into Dox to establish a heart failure model. Then, different groups of mice were administered either PBS, adeno-associated virus (AAV)-vector, AAV-miR-200b-inhibitor or TSC-Exos via tail vein injection. Then, the cardiac function, cardiac fibrosis and cardiomyocyte apoptosis in each group were evaluated, and the downstream molecular mechanism was explored. TSC-Exos and miR-200b inhibitor both decreased primary cardiomyocyte apoptosis. Similarly, mice receiving TSC-Exos and AAV-miR-200b inhibitor exhibited improved cardiac function, accompanied by reduced apoptosis and inflammation. The bioinformatic prediction and luciferase reporter results confirmed that Zeb1 was a downstream target of miR-200b and had an antiapoptotic effect. TSC-Exos attenuated doxorubicin-induced cardiac injury by playing antiapoptotic and anti-inflammatory roles. The underlying mechanism could be an increase in Zeb1 expression by the inhibition of miR-200b expression. In summary, this study sheds new light on the application of TSC-Exos as a potential therapeutic tool for heart failure.

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