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Cardiomyocytes and mToR

Bin Dong, Chen Liu, Ruicong Xue, Yan Wang, Yu Sun, Zhuomin Liang, Wendong Fan, Jingzhou Jiang, Jingjing Zhao, Qiao Su, Gang Dai, Yugang Dong, Huiling Huang
Cardiac hypertrophy is a pathophysiological response to various pathological stresses and ultimately leads to heart failure. Oxidative stress is one of the critical processes involved in hypertrophy development. Fisetin, a small molecular flavonoid, has been shown to have anti-oxidative, anti-proliferative and anti-inflammatory properties. However, the effect of fisetin on cardiac hypertrophy remains unknown. In our present study, we showed that fisetin inhibited pressure overload-induced cardiac hypertrophy, improved cardiac function in vivo and suppressed phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro...
September 1, 2018: Journal of Nutritional Biochemistry
Jinjing Yang, Jiyao Xu, Xuebin Han, Hao Wang, Yuean Zhang, Jin Dong, Yongzhi Deng, Jingping Wang
Background: Lysophosphatidic acid (LPA), as a phospholipid signal molecule, participates in the regulation of various biological functions. Our previous study demonstrated that LPA induces cardiomyocyte hypertrophy in vitro ; however, the functional role of LPA in the post-infarct heart remains unknown. Growing evidence has demonstrated that autophagy is involved in regulation of cardiac hypertrophy. The aim of the current work was to investigate the effects of LPA on cardiac function and hypertrophy during myocardial infarction (MI) and determine the regulatory role of autophagy in LPA-induced cardiomyocyte hypertrophy...
2018: Frontiers in Physiology
Jinghai Hua, Zhanghua Liu, Zuheng Liu, Dongqi An, Wenyan Lai, Qiong Zhan, Qingchun Zeng, Hao Ren, Dingli Xu
BACKGROUND Cardiac rupture often occurs after acute myocardial infarction due to complex and unclear pathogenesis. This study investigated whether metformin increases the incidence of cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1α signaling pathway. MATERIAL AND METHODS An acute myocardial infarction (MI) mouse model was established. A series of experiments involving RT-qPCR, Western blot, TUNEL staining, and Masson staining were performed in this study. RESULTS Myocardial infarction occurred, resulting in the cardiac rupture, and the expression level of PGC-1α increased in the cardiac myocardium...
October 2, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Han-Hua Zhu, Xian-Tao Wang, Yu-Han Sun, Wen-Kai He, Jia-Bao Liang, Bing-Hai Mo, Lang Li
BACKGROUND/AIMS: Microvascular obstruction (MVO), an undesirable complication of percutaneous coronary intervention, is independently associated with adverse left ventricle remodeling and poor prognosis after acute myocardial infarction. Hypoxia and oxidative stress major roles in the pathophysiology of MVO. Pim1 serves an important protective role in the ischemic myocardium, but the underlying mechanisms remain poorly defined. Autophagy in early hypoxia or during moderate oxidative stress has been demonstrated to protect the myocardium...
2018: Cellular Physiology and Biochemistry
Wei You, Zhiming Wu, Fei Ye, Xiangqi Wu
The mTORC1-dependent signaling pathway is mainly involved in the adverse left ventricular remodeling (ALVR) process after myocardial infarction (MI). However, whether mTORC1 inhibition by cardamonin attenuates ALVR after MI is still not reported. Twenty mice were randomly assigned into three groups: sham group (10 ml/kg/day PBS, n=6), model group (MI and 10 ml/kg/day PBS, n=7) and cardamonin-treated group (MI and 20 mg/kg/day cardamonin, n=7). All groups received an intraperitoneal injection accordingly for two weeks...
September 1, 2018: Die Pharmazie
Hong Zhu, Wei Cao, Peng Zhao, Jieyu Wang, Yuying Qian, Yun Li
Hyperosmotic stress may be initiated during a diverse range pathological circumstances, which in turn results in tissue damage. In this process, the activation of survival signaling, which has the capacity to restore cell homeostasis, determines cell fate. Autophagy is responsible for cell survival and is activated by various pathological stimuli. However, its interplay with hyperosmotic stress and its effect on terminally differentiated cardiac myocytes is unknown. Nuclear factor of activated T‑cells 5 (NFAT5), an osmo‑sensitive transcription factor, mediates the expression of cell survival associated‑genes under hyperosmotic conditions...
September 12, 2018: International Journal of Molecular Medicine
Joseph C Godoy, Ingrid R Niesman, Anna R Busija, Adam Kassan, Jan M Schilling, Anna Schwarz, Erika A Alvarez, Nancy D Dalton, John C Drummond, David M Roth, Georgios Kararigas, Hemal H Patel, Alice E Zemljic-Harpf
Statins, which reduce LDL-cholesterol by inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are among the most widely prescribed drugs. Skeletal myopathy is a known statin-induced adverse effect associated with mitochondrial changes. We hypothesized that similar effects would occur in cardiac myocytes in a lipophilicity-dependent manner between 2 common statins: atorvastatin (lipophilic) and pravastatin (hydrophilic). Neonatal cardiac ventricular myocytes were treated with atorvastatin and pravastatin for 48 h...
August 31, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sukka Santosh Reddy, Heena Agarwal, Manoj Kumar Barthwal
Cilostazol (Ciloz) a potent Type III phosphodiesterase inhibitor is effective against inflammation, insulin resistance and cardiomyopathy. However, the effect of Ciloz on obesity-associated left ventricular diastolic dysfunction has not been explored yet. Hence, we examined the effect of Ciloz on cardiac remodelling and dysfunction in non-obese and obese-insulin resistant mice infused with AngiotensinII (AngII). Male C57BL/6 J mice were initially subjected to 19 weeks of chow or high fat diet (HFD) regimen and thereafter animals were randomised for AngII (1500 ng/kg/min, s...
August 20, 2018: Journal of Molecular and Cellular Cardiology
Ru-Li Li, Si-Si Wu, Yao Wu, Xiao-Xiao Wang, Hong-Ying Chen, Juan-Juan Xin, He Li, Jie Lan, Kun-Yue Xue, Xue Li, Cai-Li Zhuo, Yu-Yan Cai, Jin-Han He, Heng-Yu Zhang, Chao-Shu Tang, Wang Wang, Wei Jiang
In hypertrophic hearts, autophagic flux insufficiency is recognized as a key pathology leading to maladaptive cardiac remodeling and heart failure. This study aimed to illuminate the cardioprotective role and mechanisms of a new myokine and adipokine, irisin, in cardiac hypertrophy and remodeling. Adult male wild-type, mouse-FNDC5 (irisin-precursor)-knockout and FNDC5 transgenic mice received 4 weeks of transverse aortic constriction (TAC) alone or combined with intraperitoneal injection of chloroquine diphosphate (CQ)...
August 2018: Journal of Molecular and Cellular Cardiology
Dan Shao, Outi Villet, Zhen Zhang, Sung Won Choi, Jie Yan, Julia Ritterhoff, Haiwei Gu, Danijel Djukovic, Danos Christodoulou, Stephen C Kolwicz, Daniel Raftery, Rong Tian
Glucose and branched-chain amino acids (BCAAs) are essential nutrients and key determinants of cell growth and stress responses. High BCAA level inhibits glucose metabolism but reciprocal regulation of BCAA metabolism by glucose has not been demonstrated. Here we show that glucose suppresses BCAA catabolism in cardiomyocytes to promote hypertrophic response. High glucose inhibits CREB stimulated KLF15 transcription resulting in downregulation of enzymes in the BCAA catabolism pathway. Accumulation of BCAA through the glucose-KLF15-BCAA degradation axis is required for the activation of mTOR signaling during the hypertrophic growth of cardiomyocytes...
July 26, 2018: Nature Communications
Chengxi Zhang, Sinian Pan, Ayipaxa Aisha, Minawaer Abudoukelimu, Leile Tang, Yesheng Ling
This study aimed to investigate whether recombinant human brain natriuretic peptide (rhBNP) regulated hypoxia-induced injury in H9c2 cardiomyocytes through lncRNA EGOT. H9c2 cardiomyocytes were cultured under normoxia and hypoxia (21% and 3% O2 ) conditions, and whether hypoxia induced injury by assessing cell viability, apoptosis and autophagy. H9c2 cells were then treated with different doses of exogenous rhBNP (200, 600 and 900 nmol/L, respectively) and the effects of rhBNP on hypoxia-induced injury in H9c2 cells as well as the expression of EGOT were studied...
September 10, 2018: Biochemical and Biophysical Research Communications
Asli F Ceylan, Shuyi Wang, Machender R Kandadi, Jie Chen, Yinan Hua, Zhaohui Pei, Sreejayan Nair, Jun Ren
Endothelin (ET)-1 is implicated in the pathophysiology of cardiovascular diseases although its role in obesity anomalies has not been fully elucidated. This study was designed to examine the impact of ET-1 receptor A (ETA ) ablation on obesity-induced changes in cardiac geometry and contractile function, as well as the mechanisms involved with a focus on autophagy. Cardiomyocyte-specific ETA receptor knockout (ETAKO) and WT mice were fed either low-fat (10% calorie from fat) or high-fat (45% calorie from fat) diet for 24 weeks...
October 2018: Biochimica et biophysica acta. Molecular basis of disease
Yao Qing, Xu Dong, Li Hongli, Liu Yanhui
BACKGROUND: Berberine has been verified to protect the heart from ischemia/reperfusion injury through animal experiments. However, the cardioprotective properties of berberine have not been established fully. This study was aimed at investigating whether berberine is cardioprotective in vivo and in vitro. METHODS: In the cardiomyoblast cells, the autophagosomes were observed by immunostaining. The apoptosis was detected by a flow cytometry. Beclin-1, LC3-II/I, adenosine monophosphate-activated protein kinase (AMPK), and mTOR in cardiomyocytes were detected by Western blot...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ying Luo, Zhiqiang Sun, Pengfei Hu, Yuanhong Wu, Weiwei Yu, Shuwei Huang
Objective: Descurainia sophia (L.) Webb ex Prantl (DS) is a traditional Chinese medicine. Our current study was to evaluate the effect of DS on ventricular remodeling in chronic heart failure (HF) rats and its underlying mechanism. Methods: The rat chronic heart failure model induced by suprarenal abdominal aortic coarctation surgery. The survival rats were randomly divided into 3 groups: the sham group (n=6), the HF group (n=6), and the HF+DS group (n=6). After 3 months of drug intervention, we examined the effects of DS by Sirius Red staining, electron microscopy, echocardiography, hemodynamic measurement, and TUNEL and explored the underlying mechanism by Western blotting...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Nicola Manzella, Yohan Santin, Damien Maggiorani, Hélène Martini, Victorine Douin-Echinard, Joao F Passos, Frank Lezoualc'h, Claudia Binda, Angelo Parini, Jeanne Mialet-Perez
Cellular senescence, the irreversible cell cycle arrest observed in somatic cells, is an important driver of age-associated diseases. Mitochondria have been implicated in the process of senescence, primarily because they are both sources and targets of reactive oxygen species (ROS). In the heart, oxidative stress contributes to pathological cardiac ageing, but the mechanisms underlying ROS production are still not completely understood. The mitochondrial enzyme monoamine oxidase-A (MAO-A) is a relevant source of ROS in the heart through the formation of H2 O2 derived from the degradation of its main substrates, norepinephrine (NE) and serotonin...
October 2018: Aging Cell
Wenliang Zhong, Wen Jin, Shanghua Xu, Yanqing Wu, Shunxiang Luo, Minlie Liang, Lianglong Chen
BACKGROUND: Pioglitazone has been widely used as an insulin-sensitizing agent for improving glycemic control in patients with type 2 diabetes mellitus. However, cardiovascular risk and protective effects of pioglitazone remain controversial. OBJECTIVES: In this study, we investigated whether pioglitazone affects cardiomyocyte apoptosis and hypertrophy by regulating the VEGFR-2 signaling pathway. METHODS: Cardiomyocytes were enzymatically isolated from 1- to 3-day-old Sprague-Dawley rat ventricles...
August 2018: Arquivos Brasileiros de Cardiologia
Shanshan Fu, Linlin Chen, Yizhang Wu, Ying Tang, Lu Tang, Yongkang Zhong, Siyi Wang, Haiqiong Liu, Xianbao Wang, Aihua Chen
Gastrodin (GAS), a monomeric component exacted from the herb Gastrodia elata Bl, may have cardioprotective effects during injury caused by myocardial ischemia/reperfusion (I/R). For the significant role of autophagy in I/R process, we targeted to explore whether autophagy was contributing to the GAS-induced protective effects during I/R procedure. Male C57BL/6 mice were subjected to reversible left coronary artery ligation and cultured neonatal rat cardiomyocytes (NRCs) exposed to hypoxia were preconditioned with GAS prior to ischemia or hypoxia, following reperfusion for 2 h or re-oxygennation for 3 h respectively...
September 18, 2018: Biochemical and Biophysical Research Communications
Jung Hyun Park, Hyeong Jun Ku, Jae Kyeom Kim, Jeen-Woo Park, Jin Hyup Lee
Heart failure is a frequent unfavorable outcome of pathological cardiac hypertrophy. Recent increase in dietary fructose consumption mirrors the rise in prevalence of cardiovascular diseases such as cardiac hypertrophy leading to concerns raised by public health experts. Mitochondria, comprising 30% of cardiomyocyte volume, play a central role in modulating redox-dependent cellular processes such as metabolism and apoptosis. Furthermore, mitochondrial dysfunction is a key cause of pathogenesis of fructose-induced cardiac hypertrophy...
June 21, 2018: Scientific Reports
Liang Qin, Shuxia Fan, Rongbo Jia, Yongxuan Liu
AIM: Myocardial ischemia (MI) is a leading cause of morbidity and mortality which makes the prevention and control of MI tremendously important. We aimed to explore the functional roles of ginsenoside (Gin) Rg1 in cardiomyocytes under hypoxia and to clarify underlying mechanisms. MAIN METHODS: Hypoxia-induced H9c2 cell injury was evaluated by alterations of cell viability, apoptosis and autophagy. Then, effects of Gin Rg1 on hypoxia-induced cell injury were measured...
June 1, 2018: Die Pharmazie
Zhidan Chen, Yang Li, Guoliang Jiang, Chunjie Yang, Ying Wang, Xiang Wang, Bo Fang, Guoping Zhang, Yongxin Sun, Juying Qian, Hui Gong, Yunzeng Zou
Lipoprotein receptor-related protein 6 (LRP6) binds to Wnt ligands to transduce signal by stabilization of β-catenin, which has been involved in the regulation of embryonic development and metabolism et al. Here, we observed LRP6 decreased in human hearts with dilated cardiomyopathy (DCM), and it also decreased in cultured cardiomyocytes under glucose- deprivation (GD). Knockdown of LRP6 greatly inhibited cell viability in cardiomyocytes under GD, but it didn't induce the effect in cardiomyocytes at baseline...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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