scholarly journals Cholinergic Signaling Exerts Protective Effects in Models of Sympathetic Hyperactivity-Induced Cardiac Dysfunction

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e100179 ◽  
Author(s):  
Mariana Gavioli ◽  
Aline Lara ◽  
Pedro W. M. Almeida ◽  
Augusto Martins Lima ◽  
Denis D. Damasceno ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Protective Effects ◽  
Sympathetic Hyperactivity ◽  
Cholinergic Signaling

Melatonin as an effective protector against doxorubicin-induced cardiotoxicity

2002 ◽  
Vol 283 (1) ◽  
pp. H254-H263 ◽  
Author(s):  
Xuwan Liu ◽  
Zhongyi Chen ◽  
Chu Chang Chua ◽  
Yan-Shan Ma ◽  
George A. Youngberg ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Coronary Flow ◽  
Antitumor Effect ◽  
Left Ventricular ◽  
Protective Effects ◽  
Ultrastructural Alterations ◽  
Animal Survival ◽  
Developed Pressure ◽  
Almost All

The present study was designed to explore the protective effects of melatonin and its analogs, 6-hydroxymelatonin and 8-methoxy-2-propionamidotetralin, on the survival of doxorubicin-treated mice and on doxorubicin-induced cardiac dysfunction, ultrastructural alterations, and apoptosis in mouse hearts. Whereas 60% of the mice treated with doxorubicin (25 mg/kg ip) died in 5 days, almost all the doxorubicin-treated mice survived when melatonin or 6-hydroxymelatonin (10 mg/l) was administered in their drinking water. Perfusion of mouse hearts with 5 μM doxorubicin for 60 min led to a 50% suppression of heart rate × left ventricular developed pressure and a 50% reduction of coronary flow. Exposure of hearts to 1 μM melatonin or 6-hydroxymelatonin reversed doxorubicin-induced cardiac dysfunction. 8-Methoxy-2-propionamidotetralin had no protective effects on animal survival and on in vitro cardiac function. Infusion of melatonin or 6-hydroxymelatonin (2.5 μg/h) significantly attenuated doxorubicin-induced cardiac dysfunction, ultrastructural alterations, and apoptosis in mouse hearts. Neither melatonin nor 6-hydroxymelatonin compromised the antitumor activity of doxorubicin in cultured PC-3 cells. These results suggest that melatonin protect against doxorubicin-induced cardiotoxicity without interfering with its antitumor effect.

Protective effects of propionyl-L-carnitine on cardiac dysfunction in diabetes

1992 ◽  
Vol 24 ◽  
pp. 228
Author(s):  
Tatsuaki Matsubara ◽  
Ryuya Terada ◽  
Nigishi Hotta ◽  
Nobuo Sakamoto
Keyword(s):  
Cardiac Dysfunction ◽  
Protective Effects

Role of PI3K/AKT/mTOR Pathway Associated Oxidative Stress and Cardiac Dysfunction in Takotsubo Syndrome

2020 ◽  
Vol 17 (1) ◽  
pp. 35-43
Author(s):  
Shan Mao ◽  
Xianghong Luo ◽  
Yu Li ◽  
Chaorong He ◽  
Fuhua Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Cardiac Injury ◽  
Protective Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Protective Effects ◽  
Takotsubo Syndrome ◽  
Akt Inhibitor

Introduction: Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, but the accurate cause of this syndrome is still unknown. Methods: β-adrenergic agonist isoproterenol (ISO) is used to establish the TTS rats model. TTS rats were treated with or without LY294002 or Rapamycin. The rat cardiomyoblast cell line H9C2 was subjected to infect with constitutively active Akt (myr-Akt) or dominant-negative mutant Akt (dn-Akt) and then, treated with ISO. Cell apoptosis was assessed using the Bax/ Bcl-2 ratio. In addition, reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE). Mitochondrial superoxide generation and membrane potential were assayed by MitoSOX and JC-1 fluorescence intensity. Results: ISO might induce the erratic acute cardiac dysfunction and overexpression of PI3K/AKT/mTOR. Moreover, it also increased the oxidative stress and apoptosis in TTS rats. The Akt inhibitor significantly reversed the cardiac injury effect, which triggered by ISO treatment. In H9C2 cells, the inhibition of Akt provides a protective role against ISO-induced injury by reducing oxidative stress, apoptosis and mitochondrial dysfunction. Conclusion: This study provided new insight into the protective effects of myocardial dysfunction in TTS rats via chronic inhibition of the PI3K/AKT/mTOR expression, which could reduce mitochondrial ROS and oxidative stress-induced apoptosis. PI3K/AKT/mTOR inhibitor could be a therapeutic target to treat cardiovascular dysfunction induced by stress cardiomyopathy.

scholarly journals Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction

2021 ◽  
Vol 22 (2) ◽  
pp. 525
Author(s):  
Jaqueline S. da Silva ◽  
Tadeu L. Montagnoli ◽  
Bruna S. Rocha ◽  
Matheus L. C. A. Tacco ◽  
Sophia C. P. Marinho ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Estrogen Receptors ◽  
Cardiac Dysfunction ◽  
Clinical Aspects ◽  
Protective Effects ◽  
Potential Therapeutic Target ◽  
Cardioprotective Effects ◽  
Er Alpha ◽  
Apoptotic Effects ◽  
G Protein Coupled

Estrogen receptors (ER) mediate functions beyond their endocrine roles, as modulation of cardiovascular, renal, and immune systems through anti-inflammatory and anti-apoptotic effects, preventing necrosis of cardiomyocytes and endothelial cells, and attenuating cardiac hypertrophy. Estradiol (E2) prevents cardiac dysfunction, increases nitric oxide synthesis, and reduces the proliferation of vascular cells, yielding protective effects, regardless of gender. Such actions are mediated by ER (ER-alpha (ERα), ER-beta (ERβ), or G protein-coupled ER (GPER)) through genomic or non-genomic pathways, which regulate cardiovascular function and prevent tissue remodeling. Despite the extensive knowledge on the cardioprotective effects of estrogen, clinical studies conducted on myocardial infarction (MI) and cardiovascular diseases still include favorable and unfavorable profiles. The purpose of this review is to provide up-to-date information regarding molecular, preclinical, and clinical aspects of cardiovascular E2 effects and ER modulation as a potential therapeutic target for the treatment of MI-induced cardiac dysfunction.

scholarly journals MiR-22 Inhibition Alleviates Cardiac Dysfunction in Doxorubicin-Induced Cardiomyopathy by Targeting the sirt1/PGC-1α Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Runze Wang ◽  
Yuerong Xu ◽  
Xiaolin Niu ◽  
Yexian Fang ◽  
Dong Guo ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Poor Prognosis ◽  
Cardiac Fibrosis ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Loss Of Function ◽  
Life Threatening

Doxorubicin (DOX) cardiotoxicity is a life-threatening side effect that leads to a poor prognosis in patients receiving chemotherapy. We investigated the role of miR-22 in doxorubicin-induced cardiomyopathy and the underlying mechanism in vivo and in vitro. Specifically, we designed loss-of-function and gain-of-function experiments to identify the role of miR-22 in doxorubicin-induced cardiomyopathy. Our data suggested that inhibiting miR-22 alleviated cardiac fibrosis and cardiac dysfunction induced by doxorubicin. In addition, inhibiting miR-22 mitigated mitochondrial dysfunction through the sirt1/PGC-1α pathway. Knocking out miR-22 enhanced mitochondrial biogenesis, as evidenced by increased PGC-1α, TFAM, and NRF-1 expression in vivo. Furthermore, knocking out miR-22 rescued mitophagy, which was confirmed by increased expression of PINK1 and parkin and by the colocalization of LC3 and mitochondria. These protective effects were abolished by overexpressing miR-22. In conclusion, miR-22 may represent a new target to alleviate cardiac dysfunction in doxorubicin-induced cardiomyopathy and improve prognosis in patients receiving chemotherapy.

scholarly journals CaMKII Inhibition is a Novel Therapeutic Strategy to Prevent Diabetic Cardiomyopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Christopher R. Veitch ◽  
Amelia S. Power ◽  
Jeffrey R. Erickson
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Therapeutic Strategy ◽  
Complex Disease ◽  
Positive Impact ◽  
Critical Examination ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Camkii Activation ◽  
Novel Therapeutic

Increasing prevalence of diabetes mellitus worldwide has pushed the complex disease state to the foreground of biomedical research, especially concerning its multifaceted impacts on the cardiovascular system. Current therapies for diabetic cardiomyopathy have had a positive impact, but with diabetic patients still suffering from a significantly greater burden of cardiac pathology compared to the general population, the need for novel therapeutic approaches is great. A new therapeutic target, calcium/calmodulin-dependent kinase II (CaMKII), has emerged as a potential treatment option for preventing cardiac dysfunction in the setting of diabetes. Within the last 10 years, new evidence has emerged describing the pathophysiological consequences of CaMKII activation in the diabetic heart, the mechanisms that underlie persistent CaMKII activation, and the protective effects of CaMKII inhibition to prevent diabetic cardiomyopathy. This review will examine recent evidence tying cardiac dysfunction in diabetes to CaMKII activation. It will then discuss the current understanding of the mechanisms by which CaMKII activity is enhanced during diabetes. Finally, it will examine the benefits of CaMKII inhibition to treat diabetic cardiomyopathy, including contractile dysfunction, heart failure with preserved ejection fraction, and arrhythmogenesis. We intend this review to serve as a critical examination of CaMKII inhibition as a therapeutic strategy, including potential drawbacks of this approach.

scholarly journals Single-cell Transcriptome Analysis Indicates New Potential Regulation Mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2

2020 ◽  
Author(s):  
Dachun Xu ◽  
Mengqiu Ma ◽  
Yanhua Xu ◽  
Yang Su ◽  
Sang-Bing Ong ◽  
...  
Keyword(s):  
Heart Failure ◽  
Single Cell ◽  
Natriuretic Peptides ◽  
Cardiac Dysfunction ◽  
Feedback Loop ◽  
Gene Expression Pattern ◽  
Case Series ◽  
Regulation Mechanism ◽  
High Morbidity ◽  
Protective Effects

AbstractThe coronavirus disease 2019 (COVID-19) has resulted in high morbidity and mortality worldwide since December 2019. Recent studies showed that patients with previous heart disease, especially heart failure (HF), whose plasma Natriuretic Peptides (NPs) concentrations are higher, were more susceptible to SARS-CoV-2 infection. In this study, we retrospectively analyzed single-center case series of 91 patients with COVID-19 in China. 46 (50.5%) patients exhibited cardiac dysfunction as indicated by elevated Natriuretic Peptides B (BNP) levels. Moreover, the results indicate that patients with cardiac dysfunction had higher mortality than those without cardiac dysfunction. Nonetheless, it remains unclear as to how the virus infects the heart, especially in HF patients and why a higher level of BNP in the heart dampen inflammation. Angiotensin-converting enzyme 2 (ACE2), the critical host cellular receptor of SARS-CoV-2, expresses in different organs. Still, its cellular distribution in the human heart, especially in patients with HF remains unclear. Thus, we investigated ACE2 gene expression pattern in single-cell RNA sequence (scRNA-seq) data of hearts from normal adults versus patients with HF. Our results indicate that ACE2 is predominantly enriched in cardiomyocytes (CMs), endothelial cells, fibroblasts and smooth muscle cells in normal heart. Not only ACE2+ CMs, but also expression of ACE2 are significantly boosted in CMs of patients with HF. Also, genes related to virus entry, virus replication and suppression of IFN-γ signaling besides ACE2 were up-regulated in HF patient, mainly in CMs, indicating the higher susceptibility to SARS-CoV-2 infection. Interestingly, NPs are significantly up-regulated in ACE2-postive (ACE2+) ventricular myocytes and share the upstream transcription factor. ACE2 and NPs can form a negative feedback loop with protective effects. But it maybe turns into a positive feedback loop by virus and ineffective NPs, which lead to severe prognosis. In summary, the increased expression of ACE2, NPs during HF predisposes to SARS-CoV-2 infection. Modulating the levels of ACE2, NPs therefore may potentially be a novel therapeutic target to prevent the SARS-CoV-2 infection.

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