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Cardiac autophagy

Ji Hye Park, Sung Hyun Choi, Hyungtae Kim, Seung Taek Ji, Woong Bi Jang, Jae Ho Kim, Sang Hong Baek, Sang Mo Kwon
Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs...
October 9, 2016: International Journal of Molecular Sciences
Adam Kassan, Uyen Pham, Quynhmy Nguyen, Melissa E Reichelt, Eunbyul Cho, Piyush M Patel, David M Roth, Brian P Head, Hemal H Patel
Autophagy is a dynamic recycling process responsible for the breakdown of misfolded proteins and damaged organelles, providing nutrients and energy for cellular renovation and homeostasis. Loss of autophagy is associated with cardiovascular diseases. Caveolin-3 (Cav-3), a muscle-specific isoform, is a structural protein within caveolae and is critical to stress adaptation in the heart. Whether Cav-3 plays a role in regulating autophagy to modulate cardiac stress responses remains unknown. In the present study, we used HL-1 cells, a cardiac muscle cell line, with stable Cav-3 knockdown (Cav-3 KD) and Cav-3 over-expression (Cav-3 OE) to study the impact of Cav-3 in regulation of autophagy...
October 5, 2016: American Journal of Physiology. Cell Physiology
Shivika S Gupta, Matthew R Zeglinski, Sunil G Rattan, Natalie M Landry, Saeid Ghavami, Jeffrey T Wigle, Thomas Klonisch, Andrew J Halayko, Ian M C Dixon
The incidence of heart failure with concomitant cardiac fibrosis is very high in developed countries. Fibroblast activation in heart is causal to cardiac fibrosis as they convert to hypersynthetic cardiac myofibroblasts. There is no known treatment for cardiac fibrosis. Myofibroblasts contribute to the inappropriate remodeling of the myocardial interstitium, which leads to reduced cardiac function and ultimately heart failure. Elevated levels of autophagy have been linked to stress-induced ventricular remodeling and other cardiac diseases...
October 1, 2016: Oncotarget
Jianqiang Hu, Lei Zhang, Yang Yang, Yanjie Guo, Yanhong Fan, Mingming Zhang, Wanrong Man, Erhe Gao, Wei Hu, Russel J Reiter, Haichang Wang, Dongdong Sun
Melatonin reportedly protects against several cardiovascular diseases including ischemia/reperfusion (I/R), atherosclerosis and hypertension. The present study investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy, apoptosis and mitochondrial injury in the context of MI. We demonstrated that melatonin significantly alleviated cardiac dysfunction after MI. Four weeks after MI, echocardiography and Masson staining indicated that melatonin notably mitigated adverse left ventricle remodeling...
October 1, 2016: Journal of Pineal Research
Antoine Heni Chaanine, Erik Kohlbrenner, Scott I Gamb, Adam J Guenzel, Katherine A Klaus, Ahmed U Fayyaz, K Sreekumaran Nair, Roger J Hajjar, Margaret M Redfield
The Forkhead box O3a (FOXO3a) transcription factor has been shown to regulate glucose metabolism, muscle atrophy and cell death in post-mitotic cells. Its role in regulating mitochondrial and myocardial function is not well studied. Based on previous work, we hypothesized that FOXO3a, through BNIP3, modulates mitochondrial morphology and function in HF. We modulated the FOXO3a-BNIP3 pathway in normal and phenylephrine (PE) stressed adult cardiac myocytes (ACM) in vitro and developed a cardiotropic adeno-associated virus serotype 9 encoding dominant-negative FOXO3a (AAV9...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Yuanyuan Hao, Qun Lu, Guodong Yang, Aiqun Ma
BACKGROUND: Myocardial remodeling and cardiac dysfunction prevention may represent a therapeutic approach to reduce mortality in patients with myocardial infarction (MI). We investigated the effects of Lin28a in experimental MI models, as well as the mechanisms underlying these effects. METHODS: Left anterior descending (LAD) coronary artery ligation was used to construct an MI-induced injury model. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of Lin28a against MI-induced injury...
October 28, 2016: Biochemical and Biophysical Research Communications
Mingyi Zhao, Ping Zhu, Masayuki Fujino, Yoshiaki Nishio, Jimei Chen, Hidenori Ito, Kiwamu Takahashi, Motowo Nakajima, Tohru Tanaka, Lingling Zhao, Jian Zhuang, Xiao-Kang Li
BACKGROUND: Hypoxia causes cardiac disease via oxidative stress and mitochondrial dysfunction. 5-Aminolevulinic acid in combination with sodium ferrous citrate (ALA/SFC) has been shown to up-regulate heme oxygenase-1 (HO-1) and decrease macrophage infiltration and renal cell apoptosis in renal ischemia injury mice. However, its underlying mechanism remains largely unknown. The aim of this study was to investigate whether ALA/SFC could protect cardiomyocytes from hypoxia-induced apoptosis by autophagy via HO-1 signaling...
October 28, 2016: Biochemical and Biophysical Research Communications
Jihoon Nah, Álvaro F Fernández, Richard N Kitsis, Beth Levine, Junichi Sadoshima
No abstract text is available yet for this article.
September 30, 2016: Circulation Research
Shashi Kumar Gupta, Ariana Foinquinos, Sabrina Thum, Janet Remke, Karina Zimmer, Christophe Bauters, Pascal de Groote, Reinier A Boon, Leon J de Windt, Sebastian Preissl, Lutz Hein, Sandor Batkai, Florence Pinet, Thomas Thum
BACKGROUND: Aging populations show higher incidences of myocardial infarction (MI) and heart failure (HF). Cardiac remodeling post-MI leads to progressive impaired cardiac function caused by a disarray of several processes including derailed autophagy. Microribonucleic acids (miRNAs) are known to be key players in cardiovascular disease but their involvement in cardiac autophagy and aging is not well understood. OBJECTIVES: This study sought to identify new miRNA candidates that regulate cardiac autophagy and aging...
October 4, 2016: Journal of the American College of Cardiology
Qihai Xie, Tong Wei, Chenglin Huang, Penghao Liu, Mengwei Sun, Weili Shen, Pingjin Gao
NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d)...
September 30, 2016: Scientific Reports
Zhouqing Huang, Shengjie Wu, Fanqi Kong, Xueli Cai, Bozhi Ye, Peiren Shan, Weijian Huang
MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)-induced injury. Here, we investigated the function of miR-21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR-21 in regulating autophagy, H9c2 cells were divided into the following six groups: control group, H/R group, (miR-21+ H/R) group, (miR-21-negative control + H/R) group, (BEZ235+ H/R) group and (miR-21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs...
September 29, 2016: Journal of Cellular and Molecular Medicine
Jie Lin, Lei Zhang, Mingming Zhang, Jianqiang Hu, Tingting Wang, Yu Duan, Wanrong Man, Bin Wu, Jiaxu Feng, Lei Sun, Congye Li, Rongqing Zhang, Haichang Wang, Dongdong Sun
Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function...
September 29, 2016: Scientific Reports
Elisa Da Silva-Ferrada, Teresa M Ribeiro-Rodrigues, Manuel S Rodríguez, Henrique Girão
Heart proteostasis relies on a complex and integrated network of molecular processes surveilling organ performance under physiological and pathological conditions. For this purpose, cardiac cells depend on the correct function of their proteolytic systems, such as the ubiquitin-proteasome system (UPS), autophagy and the calpain system. Recently, the role of protein SUMOylation (an ubiquitin-like modification), has emerged as important modulator of cardiac proteostasis, which will be the focus of this review...
October 2016: International Journal of Biochemistry & Cell Biology
Vivek Kaushik, Juan Sebastian Yakisich, Neelam Azad, Yogesh Kulkarni, Rajkumar Venkatadri, Clayton Wright, Yon Rojanasakul, Anand Krishnan V Iyer
Lung cancer is a leading cause of cancer-related death in the United States. While several drugs have been developed that target individual biomarkers, their success has been limited due to intrinsic or acquired resistance for the specific targets of such drugs. A more effective approach is to target multiple pathways that dictate cancer progression. Cardiac glycosides demonstrate such multimodal effects on cancer cell survival, and our aim was to evaluate the effect of two naturally occurring monosaccaridic cardiac glycosides - Convallatoxin and Peruvoside on lung cancer cells...
September 23, 2016: Journal of Cellular Physiology
Yee-Ki Lee, Yu Jiang, Xin-Ru Ran, Yee-Man Lau, Kwong-Man Ng, Wing-Hon Kevin Lai, Chung-Wah Siu, Hung-Fat Tse
Laminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively...
2016: Stem Cell Research & Therapy
Nan Hu, Jun Ren, Yingmei Zhang
Insulin resistance contributes to the high prevalence of type 2 diabetes mellitus, leading to cardiac anomalies. Emerging evidence depicts a pivotal role for mitochondrial injury in oxidative metabolism and insulin resistance. Mitochondrial aldehyde dehydrogenase (ALDH2) is one of metabolic enzymes detoxifying aldehydes although its role in insulin resistance remains elusive. This study was designed to evaluate the impact of ALDH2 overexpression on insulin resistance-induced myocardial damage and mechanisms involved with a focus on autophagy...
September 12, 2016: Oncotarget
Lei Lai, Ningfu Wang, Gangjie Zhu, Xu Duan, Feng Ling
OBJECTIVE: miRNAs are a class of small non-coding RNAs that has been proved to be involved in cardioprotection. The present study was to detect role of miR-30e in cardiac-protective action of ACE2 (angiotensin-converting enzyme 2). METHODS: Sprague Dawley rats were divided into 3 groups and received treatment for a total of 6weeks: group1, normal rats; group2, Doxorubicin-induced heart cardiomyopathy (DHC) rats; and group3, rhACE2 (recombinant human ACE2) treated DHC rats...
September 12, 2016: Life Sciences
A Reis-Mendes, A S Gomes, R A Carvalho, F Carvalho, F Remião, M Pinto, M L Bastos, E Sousa, V M Costa
Mitoxantrone (MTX) is an antineoplastic agent used to treat several types of cancers and on multiple sclerosis, which shows a high incidence of cardiotoxicity. Still, the underlying mechanisms of MTX cardiotoxicity are poorly understood and the potential toxicity of its metabolites scarcely investigated. Therefore, this work aimed to synthesize the MTX-naphthoquinoxaline metabolite (NAPHT) and to compare its cytotoxicity to the parent compound in 7-day differentiated H9c2 cells using pharmacological relevant concentrations (0...
September 14, 2016: Archives of Toxicology
Xun Yuan, Yi-Chuan Xiao, Gui-Ping Zhang, Ning Hou, Xiao-Qian Wu, Wen-Liang Chen, Jian-Dong Luo, Gen-Shui Zhang
Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14 days after CQ (ip 60 mg/kg/d) administration...
2016: Drug Design, Development and Therapy
Theodora Tzanavari, Aimilia Varela, Stamatis Theocharis, Elpinickie Ninou, Alkistis Kapelouzou, Dennis V Cokkinos, Maria I Kontaridis, Katia P Karalis
BACKGROUND AND PURPOSE: Metformin administration is associated with myocardial protection during ischemia and/or reperfusion, possibly via inhibition of inflammatory responses in the heart. Exposure to pathogens, in addition to the activation of the immune system and the associated metabolic dysfunction, often results in compromised myocardial function. We examined whether metformin administration could maintain the normal myocardial function in experimental moderate Gram negative infection, induced by lipopolysaccharide (LPS) administration...
October 2016: Metabolism: Clinical and Experimental
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