Melatonin differentially regulates pathological and physiological cardiac hypertrophy: Crucial role of circadian nuclear receptor RORα signaling

Xu, Longwei; Su, Yuanyuan; Zhao, Yichao; Sheng, Xincheng; Tong, Renyang; Ying, Xiaoying; Gao, Liang; Ji, Qingqi; Gao, Yu; Yang, Yan; Yuan, Ancai; Wu, Fujian; Lan, Feng; Pu, Jun

doi:10.1111/jpi.12579

Cited by 61 publications

(39 citation statements)

References 56 publications

(95 reference statements)

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“…Cardiac hypertrophy is an important characteristic of many cardiovascular diseases; it usually results in heart failure and is a major cause of mortality worldwide [1]. Cardiac hypertrophy results in myocardial adverse remodeling, which includes myocardial fibrosis, cardiomyocyte death, and cardiac dysfunction [2][3][4]. Although remarkable efforts have been made by researchers to unveil the molecular pathophysiology and develop effective methods to prevent or reverse cardiac hypertrophy, to date there has no satisfactory clinical therapy.…”

Section: Introductionmentioning

confidence: 99%

Wnt-C59 Attenuates Pressure Overload-Induced Cardiac Hypertrophy via Interruption of Wnt Pathway

Zhao

Liu

et al. 2020

Med Sci Monit

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Departmental sources Background: Cardiac hypertrophy usually results in heart failure and is an important cause of mortality worldwide. Wnt/bcatenin signaling pathway hyper-activation is involved in the pathogenesis and progression of cardiac hypertrophy. Wnt-C59 is a small molecular compound, which strongly and specifically targets at Porcupine to pharmacologically inhibit Wnt palmitoylation, secretion, and other biological activities. However, the role of Wnt-C59 in cardiac hypertrophy remains unknown. Material/Methods: We performed transverse aortic constriction (TAC) in adult male mice to induce pressure overload and establish an in vivo model of cardiac hypertrophy. Angiotensin II (Ang-II) was utilized to culture cardiomyocyte to establish a model of in vitro cardiomyocyte hypertrophy. Daily administration of Porcupine inhibitor Wnt-C59 was performed for 4 weeks after TAC surgery. Results: Wnt-C59 significantly improved cardiac function and enhanced survival of mice subjected to TAC surgery. Histologically, Wnt-C59 attenuated TAC-induced increase in heart mass, cross-section area of cardiomyocyte, cardiac fibrosis, cardiomyocyte apoptosis, and expression of the hypertrophic biomarkers b-MHC, ANP, and BNP. TAC-induced oxidative stress was also ameliorated by Wnt-C59. Wnt-C59 attenuated Ang-II-induced in vitro cardiomyocyte hypertrophy, as indicated by decreased cell size and lower expression of ANP, BNP, and b-MHC. Moreover, Wnt/b-catenin activation was blocked by Wnt-C59 in cardiac hypertrophy, as indicated by decreased protein expression of Wnt3a and b-catenin and the Wnt target genes cyclin D1 and c-Myc. Conclusions: Collectively, Porcupine inhibitor Wnt-C59 attenuates pressure overload-induced cardiac hypertrophic via interruption of the Wnt/b-catenin signaling pathway, and it might be a promising drug for patients with cardiac hypertrophy.

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Section: Introductionmentioning

confidence: 99%

Wnt-C59 Attenuates Pressure Overload-Induced Cardiac Hypertrophy via Interruption of Wnt Pathway

Zhao

Liu

et al. 2020

Med Sci Monit

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“…From the survival analysis, our results were consistent with previous studies. Actually, the etiology of AMI was complicated, included alternated lipid metabolism, inflammatory reaction, oxidation injury, and other pathological processes [29][30][31][32]. Herein, we hypothesized that the NHR, a novel index composed of inflammatory cell and lipid cholesterol, might reflect the inflammatory status and the lipid metabolism more comprehensively.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil to high-density lipoprotein ratio has a superior prognostic value in elderly patients with acute myocardial infarction: a comparison study

Huang

Chen

et al. 2020

Lipids Health Dis

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Background: The importance of the lipid-related biomarkers has been implicated in the pathological process and prognosis of acute myocardial infarction (AMI). Our work was conducted to discuss and compare the predictive ability of the neutrophil to high-density lipoprotein cholesterol (HDL-C) ratio (NHR) with other existing prognostic indices, for instance, the monocyte to HDL-C ratio (MHR) and the low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (LDL-C/HDL-C) in elderly patients with AMI. Methods: Our population was 528 consecutive elderly AMI patients (65-85 years) who were enrolled from Tongji Hospital and grouped according to the cutoff points which were depicted by the receiver operating characteristic (ROC). The Kaplan-Meier curves were plotted with the survival data from the follow-up to investigate the difference between cutoff point-determined groups. Moreover, we assessed the impact of NHR, MHR, LDL-C/HDL-C on the long-term mortality and recurrent myocardial infarction (RMI) with Cox proportional hazard models. Results: Mean duration of follow-up was 673.85 ± 14.32 days (median 679.50 days). According to ROC curve analysis, NHR ≥ 5.74, MHR ≥ 0.67, LDL-C/HDL-C ≥ 3.57 were regarded as high-risk groups. Kaplan-Meier analysis resulted that the high-NHR, high-MHR and high-LDL-C/HDL-C groups presented higher mortality and RMI rate than the corresponding low-risk groups in predicting the long-term clinical outcomes (log-rank test: all P < 0.050). In multivariate analysis, compared with MHR and LDL-C/HDL-C, only NHR was still recognized as a latent predictor for long-term mortality (harzard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.02 to 3.75, P = 0.044) and long-term RMI (HR: 2.23, 95% CI: 1.04 to 4.79, P = 0.040). Furthermore, the positive correlation between NHR and Gensini score (r = 0.15, P < 0.001) indicated that NHR was relevant to the severity of coronary artery to some extent.

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“…Bro-Jeppesen et al reported baseline plasma IL-6 and IL-10 levels were significantly higher in non-survivors compared with survivors [11,12]. Melatonin, an anti-oxidant and anti-inflammatory agent, improves neurological outcomes and preserves hippocampal mitochondrial function in cardiac arrest [36], which may be associated with its protection against inflammation [22,[37][38][39], myocardial ischemia-reperfusion injury [40][41][42][43], ventricular fibrillation [44], cardiac hypertrophy [45], dilated cardiomyopathy [46], and mitochondria-related disorders [47,48]. As neutralization of IL-17 rescues neuroinflammation [49], melatonin may contribute to the complex role of IL-17 signaling in ROSC [50].…”

Section: Discussionmentioning

confidence: 99%

High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience

Zhuang

Chen

Zhou

et al. 2020

BMC Cardiovasc Disord

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Background: Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines , IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post-cardiac arrest period. Methods: This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated "survivors". The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays. Results: Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC.Conclusion: These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients.Trial registration: Clinicaltrial.gov NCT02297776, 2014-11-21.

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Melatonin differentially regulates pathological and physiological cardiac hypertrophy: Crucial role of circadian nuclear receptor RORα signaling

Cited by 61 publications

References 56 publications

Wnt-C59 Attenuates Pressure Overload-Induced Cardiac Hypertrophy via Interruption of Wnt Pathway

Wnt-C59 Attenuates Pressure Overload-Induced Cardiac Hypertrophy via Interruption of Wnt Pathway

Neutrophil to high-density lipoprotein ratio has a superior prognostic value in elderly patients with acute myocardial infarction: a comparison study

High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience

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