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The Histone Demethylase JMJD1C Regulates CAMKK2-AMPK Signaling to Participate in Cardiac Hypertrophy

组蛋白去甲基化酶 JMJD1C 调节 CAMKK2-AMPK 信号参与心肌肥厚

  • 影响因子:3.22
  • DOI:10.3389/fphys.2020.00539
  • 作者列表:"Shuang Yu","Yihong Li","Hongwei Zhao","Qingdong Wang","Ping Chen
  • 发表时间:2020-06-18
Abstract

The roles of the histone demethylase JMJD1C in cardiac hypertrophy remain unknown. JMJD1C was overexpressed in hypertrophic hearts of humans and mice, whereas the histone methylation was reduced. Jmjd1c knockdown repressed the angiotensin II (Ang II)-mediated increase in cardiomyocyte size and overexpression of hypertrophic genes in cardiomyocytes. By contrast, JMJD1C overexpression promoted the hypertrophic response of cardiomyocytes. Our further molecular mechanism study revealed that JMJD1C regulated AMP-dependent kinase (AMPK) in cardiomyocytes. JMJD1C did not influence LKB1 but repressed Camkk2 expression in cardiomyocytes. Inhibition of CAMKK2 with STO609 blocked the effects of JMJD1C on AMPK. AMPK knockdown blocked the inhibitory functions of JMJD1C knockdown on Ang II-induced hypertrophic response, whereas metformin reduced the functions of JMJD1C and repressed the hypertrophic response in cardiomyocytes.

摘要

组蛋白去甲基化酶 JMJD1C 在心肌肥厚中的作用仍然未知。JMJD1C 在人和小鼠的肥大心脏中过表达,而组蛋白甲基化减少。Jmjd1c 敲除抑制血管紧张素 ⅱ (Ang ⅱ) 介导的心肌细胞大小增加和心肌细胞肥大基因的过度表达。相比之下,JMJD1C 过表达促进了心肌细胞的肥大反应。我们进一步的分子机制研究揭示了 JMJD1C 调控心肌细胞中 AMP 依赖性激酶 (AMPK)。JMJD1C 不影响 LKB1,但抑制心肌细胞 Camkk2 的表达。用 STO609 抑制 CAMKK2 阻断 JMJD1C 对 AMPK 的影响。AMPK 敲除阻断了 JMJD1C 敲除对 Ang II 诱导的心肌肥厚反应的抑制功能,而二甲双胍降低了 JMJD1C 的功能,抑制了心肌细胞的肥厚反应。

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影响因子:2.06
发表时间:2020-01-12
DOI:10.1186/s12872-019-01311-4
作者列表:["Nattawut Wongpraparut","Sarawut Siwamogsatham","Tomorn Thongsri","Pornchai Ngamjanyaporn","Arintaya Phrommintikul","Kompoj Jirajarus","Tarinee Tangcharoen","Kid Bhumimuang","Pinij Kaewsuwanna","Rungroj Krittayaphong","Rungtiwa Pongakasira","Harvey D. White"]

METHODS:Abstract Background Ischemic cardiomyopathy is a high-cost, resource-intensive public health burden that is associated with a 1-year mortality rate of about 16% in western population. Different in patient ethnicity and pattern of practice may impact the clinical outcome. We aim to determine 1-year mortality and to identify factors that significantly predicts 1-year mortality of Thai patients with ischemic cardiomyopathy. Methods This prospective multicenter registry enrolled consecutive Thai patients that were diagnosed with ischemic cardiomyopathy at 9 institutions located across Thailand. Patients with left ventricular function  75% in the left main or proximal left anterior descending artery or coronary angiography, and/or two major epicardial coronary stenoses; 2) prior myocardial infarction; 3) prior revascularization by coronary artery bypass graft or percutaneous coronary intervention; or, 4) magnetic resonance imaging pattern compatible with ischemic cardiomyopathy. Baseline clinical characteristics, coronary and echocardiographic data were recorded. The 1-year clinical outcome was pre-specified. Results Four hundred and nineteen patients were enrolled. Thirty-nine patients (9.9%) had died at 1 year, with 27 experiencing cardiovascular death, and 12 experiencing non-cardiovascular death. A comparison between patients who were alive and patients who were dead at 1 year revealed lower baseline left ventricular ejection fraction (LVEF) (26.7 ± 7.6% vs 30.2 ± 7.8%; p = 0.021), higher left ventricular end-diastolic volume (LVEDV) (185.8 ± 73.2 ml vs 155.6 ± 64.2 ml; p = 0.014), shorter mitral valve deceleration time (142.9 ± 57.5 ml vs 182.4 ± 85.7 ml; p = 0.041), and lower use of statins (94.7% vs 99.7%; p = 0.029) among deceased patients. Patients receiving guideline-recommended β-blockers had lower mortality than patients receiving non-guideline-recommended β-blockers (8.1% vs 18.2%; p = 0.05). Conclusions The results of this study revealed a 9.9% 1-year mortality rate among Thai ischemic cardiomyopathy patients. Doppler echocardiographic parameters significantly associated with 1-year mortality were LVEF, LVEDV, mitral E velocity, and mitral valve deceleration time. The use of non-guideline-recommended β-blockers rather than guideline recommended β-blockers were associated with increased with 1-year mortality. Guidelines recommended β-blockers should be preferred. Trial registration Thai Clinical Trials Registry TCTR20190722002. Registered 22 July 2019. “Retrospectively registered”.

影响因子:4.69
发表时间:2020-01-07
DOI:10.1186/s12968-019-0590-z
作者列表:["Yao-Dan Liang","Yuan-Wei Xu","Wei-Hao Li","Ke Wan","Jia-Yu Sun","Jia-Yi Lin","Qing Zhang","Xiao-Yue Zhou","Yu-Cheng Chen"]

METHODS:Abstract Background Peripartum cardiomyopathy (PPCM) is rare and potentially life-threatening; its etiology remains unclear. Imaging characteristics on cardiovascular magnetic resonance (CMR) and their prognostic significance have rarely been studied. We sought to determine CMR’s prognostic value in PPCM by using T1 and T2 mapping techniques. Methods Data from 21 PPCM patients from our CMR registry database were analyzed. The control group comprised 20 healthy age-matched females. All subjects underwent comprehensive contrast-enhanced CMR. T1 and T2 mapping using modified Look-Locker inversion recovery and T2 prep balanced steady-state free precession sequences, respectively. Ventricular size and function, late gadolinium enhancement (LGE), myocardial T1 value, extracellular volume (ECV), and T2 value were analyzed. Transthoracic echocardiography was performed at baseline and during follow-up. The recovered left ventricular ejection fraction (LVEF) was defined as LVEF ≥50% on echocardiography follow-up after at least 6 months of the diagnosis. Results CMR imaging showed that the PPCM patients had severely impaired LVEF and right ventricular ejection fraction (LVEF: 26.8 ± 10.6%; RVEF: 33.9 ± 14.6%). LGE was seen in eight (38.1%) cases. PPCM patients had significantly higher native T1 and ECV (1345 ± 79 vs. 1212 ± 32 ms, P < 0.001; 33.9 ± 5.2% vs. 27.1 ± 3.1%, P < 0.001; respectively) and higher myocardial T2 value (42.3 ± 3.7 vs. 36.8 ± 2.3 ms, P < 0.001) than did the normal controls. After a median 2.5-year follow-up (range: 8 months-5 years), six patients required readmission for heart failure, two died, and 10 showed left ventricular function recovery. The LVEF-recovered group showed significantly lower ECV (30.7 ± 2.1% vs. 36.8 ± 5.6%, P = 0.005) and T2 (40.6 ± 3.0 vs. 43.9 ± 3.7 ms, P = 0.040) than the unrecovered group. Multivariable logistic regression analysis showed ECV (OR = 0.58 for per 1% increase, P = 0.032) was independently associated with left ventricular recovery in PPCM. Conclusions Compared to normal controls, PPCM patients showed significantly higher native T1, ECV, and T2. Native T1, ECV, and T2 were associated with LVEF recovery in PPCM. Furthermore, ECV could independently predict left ventricular function recovery in PPCM.

影响因子:4.69
发表时间:2020-01-05
DOI:10.1186/s12968-019-0589-5
作者列表:["Yingxia Yang","Gang Yin","Yong Jiang","Lei Song","Shihua Zhao","Minjie Lu"]

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