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Cardiac autophagy

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https://www.readbyqxmd.com/read/28238968/changes-in-macroautophagy-chaperone-mediated-autophagy-and-mitochondrial-metabolism-in-murine-skeletal-and-cardiac-muscle-during-aging
#1
Jin Zhou, Shu Yun Chong, Andrea Lim, Brijesh K Singh, Rohit A Sinha, Adam B Salmon, Paul M Yen
Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging...
February 26, 2017: Aging
https://www.readbyqxmd.com/read/28238768/regulation-of-autophagy-by-some-natural-products-as-a-potential-therapeutic-strategy-for-cardiovascular-disorders
#2
REVIEW
Mahmoud Hashemzaei, Reza Entezari Heravi, Ramin Rezaee, Ali Roohbakhsh, Gholamreza Karimi
Autophagy is a lysosomal degradation process through which long-lived and misfolded proteins and organelles are sequestered, degraded by lysosomes, and recycled. Autophagy is an essential part of cardiomyocyte homeostasis and increases the survival of cells following cellular stress and starvation. Recent studies made clear that dysregulation of autophagy in the cardiovascular system leads to heart hypertrophy and failure. In this manner, autophagy seems to be an attractive target in the new treatment of cardiovascular diseases...
February 23, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28225086/uvrag-deficiency-exacerbates-doxorubicin-induced-cardiotoxicity
#3
Lin An, Xiao-Wen Hu, Shasha Zhang, Xiaowen Hu, Zongpei Song, Amber Naz, Zhenguo Zi, Jian Wu, Can Li, Yunzeng Zou, Lin He, Hongxin Zhu
Doxorubicin (DOX) is an effective chemotherapeutic drug in the treatment of various types of cancers. However, its clinical application has been largely limited by potential development of cardiotoxicity. Previously we have shown that ultra-violet radiation resistance-associated gene (UVRAG), an autophagy-related protein, is essential for the maintenance of autophagic flux in the heart under physiological conditions. Here, we sought to determine the role of UVRAG-mediated autophagy in DOX-induced cardiotoxicity...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#4
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28216620/aspirin-alleviates-cardiac-fibrosis-in-mice-by-inhibiting-autophagy
#5
Ping-Ping Liu, Hong-Hong Liu, Shu-Hong Sun, Xing-Xing Shi, Wan-Cheng Yang, Guo-Hai Su, Jing Zhao
Aspirin (ASA) is a cardioprotective drug with anti-cardiac fibrosis action in vivo. This study was aimed to clarify the anti-cardiac fibrosis action of ASA and the underlying mechanisms. Two heart injury models (injection of isoproterenol and ligation of the left anterior descending branch) were used in mice to induce cardiac fibrosis. The animals were treated with ASA (10 mg·kg(-1)·d(-1), ig) for 21 and 14 d, respectively. ASA administration significantly improved cardiac function, and ameliorated heart damage and fibrosis in the mice...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216152/1-25-dihydroxyvitamin-d3-prevents-the-development-of-diabetic-cardiomyopathy-in-type-1-diabetic-rats-by-enhancing-autophagy-via-inhibiting-the-%C3%AE-catenin-tcf4-gsk-3%C3%AE-mtor-pathway
#6
Huili Wei, Hua Qu, Hang Wang, Baolan Ji, Yao Ding, Dan Liu, Yang Duan, Huimin Liang, Chuan Peng, Xiaoqiu Xiao, Huacong Deng
Diabetic cardiomyopathy (DCM) can increase the risk of heart failure and death in diabetic patients. However, no effective approaches are available to prevent its progression and development. Studies have shown that vitamin D is greatly implicated in cardiac hypertrophy and fibrosis, and there is a high prevalence of vitamin D deficiency in diabetic patients. In this study, we investigated whether 1,25-Dihydroxyvitamin-D3 (1,25D3) can improve DCM through a vitamin D receptor (VDR)-dependent mechanism associated with autophagy and the β-catenin/T-cell factor/lymphoid enhancer factor (TCF4)/glycogen synthase kinase-3β (GSK-3β)/mammalian target of rapamycin (mTOR) pathway...
February 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28198521/sevoflurane-ameliorates-doxorubicin-induced-myocardial-injury-by-affecting-the-phosphorylation-states-of-proteins-in-pi3k-akt-mtor-signaling-pathway
#7
Yini Wu, Jianping Wang, Xiaoyan Yu, Dongli Li, Xin Han, Lihua Fan
BACKGROUND: The effect of sevoflurane on the doxorubicin-induced myocardial injury was explored by investigating the phosphorylation states of proteins in phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Myocardial injury rat models were induced by doxorubicin and evenly assigned into five groups according to different treatment: Doxorubicin group (DG, 200-µL saline solution), sevoflurane group (SevG, inhaled with 2...
February 15, 2017: Cardiology Journal
https://www.readbyqxmd.com/read/28194437/mitochondrial-quality-control-dysregulation-in-conditional-ho-1-mice
#8
Hagir B Suliman, Jeffrey E Keenan, Claude A Piantadosi
The heme oxygenase-1 (Hmox1; HO-1) pathway was tested for defense of mitochondrial quality control in cardiomyocyte-specific Hmox1 KO mice (HO-1[CM](-/-)) exposed to oxidative stress (100% O2). After 48 hours of exposure, these mice showed persistent cardiac inflammation and oxidative tissue damage that caused sarcomeric disruption, cardiomyocyte death, left ventricular dysfunction, and cardiomyopathy, while control hearts showed minimal damage. After hyperoxia, HO-1(CM)(-/-) hearts showed suppression of the Pgc-1α/nuclear respiratory factor-1 (NRF-1) axis, swelling, low electron density mitochondria by electron microscopy (EM), increased cell death, and extensive collagen deposition...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28181410/sestrin-1-ameliorates-cardiac-hypertrophy-via-autophagy-activation
#9
Ruicong Xue, Junyi Zeng, Yili Chen, Cong Chen, Weiping Tan, Jingjing Zhao, Bin Dong, Yu Sun, Yugang Dong, Chen Liu
Cardiac hypertrophy is one of the major risk factors of cardiovascular morbidity and mortality. Autophagy is acknowledged to be an important mechanism regulating cardiac hypertrophy. Sestrin 1, a downstream target gene of p53, has been proven to regulate autophagy. However, the role of Sestrin 1 in cardiac hypertrophy remains unknown. Our study showed that Sestrin 1 mRNA and protein expression declined in pressure overload cardiac hypertrophy and phenylephrine (PE)-induced cardiac hypertrophy. Knockdown of Sestrin 1 by RNAi deteriorated PE-induced cardiac hypertrophy, whereas the overexpression of Sestrin 1 by adenovirus transfection blunted hypertrophy...
February 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28164169/adeno-associated-virus-serotype-9-driven-expression-of-bag3-improves-left-ventricular-function-in-murine-hearts-with-left-ventricular-dysfunction-secondary-to-a-myocardial-infarction
#10
Tijana Knezevic, Valerie D Myers, Feifei Su, JuFang Wang, Jianliang Song, Xue-Qian Zhang, Erhe Gao, Guofeng Gao, Madesh Muniswamy, Manish K Gupta, Jennifer Gordon, Kristen N Weiner, Joseph Rabinowitz, Frederick V Ramsey, Douglas G Tilley, Kamel Khalili, Joseph Y Cheung, Arthur M Feldman
OBJECTIVES: The present study was undertaken to test the hypothesis that gene delivery of BCL2-Associated Athanogene 3 (BAG3) to the heart of mice with left ventricular dysfunction secondary to a myocardial infarction could enhance cardiac performance. BACKGROUND: BAG3 is a 575 amino acid protein that has pleotropic functions in the cell including pro-autophagy and anti-apoptosis. Mutations in BAG3 have been associated with both skeletal muscle dysfunction and familial dilated cardiomyopathy and BAG3 levels are diminished in non-familial heart failure...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28159361/enhanced-autophagy-by-exenatide-mitigates-doxorubicin-induced-cardiotoxicity
#11
Kyung Hye Lee, Haneul Cho, Sora Lee, Jong Shin Woo, Byung Hyun Cho, Jung Hee Kang, Yun-Mi Jeong, Xian Wu Cheng, Weon Kim
OBJECTIVES: Exenatide is a glucagon-like peptide-1 analogue that mitigates myocardial injury caused by ischemia-reperfusion injury via the survival signaling pathway. We hypothesized that exenatide would provide a protective effect in doxorubicin-induced cardiotoxicity. METHODS: H9c2 cardiomyocytes were pre-treated with exenatide followed by doxorubicin (DOX), and cell viability and intracellular reactive oxygen species (ROS) were subsequently measured. In order to determine the role of autophagy, we performed western blot as well as TUNEL and autophagosome staining...
January 27, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28151473/knockout-of-eva1a-leads-to-rapid-development-of-heart-failure-by-impairing-autophagy
#12
Shu Zhang, Xin Lin, Ge Li, Xue Shen, Di Niu, Guang Lu, Xin Fu, Yingyu Chen, Ming Cui, Yun Bai
EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28134239/a-rab5-endosomal-pathway-mediates-parkin-dependent-mitochondrial-clearance
#13
Babette C Hammerling, Rita H Najor, Melissa Q Cortez, Sarah E Shires, Leonardo J Leon, Eileen R Gonzalez, Daniela Boassa, Sébastien Phan, Andrea Thor, Rebecca E Jimenez, Hong Li, Richard N Kitsis, Gerald W Dorn Ii, Junichi Sadoshima, Mark H Ellisman, Åsa B Gustafsson
Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of mitochondria is autophagy, where damaged organelles are marked for disposal via ubiquitylation by Parkin. Here we report a novel pathway for mitochondrial elimination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early endosomes via the ESCRT machinery. Following maturation, these endosomes deliver mitochondria to lysosomes for degradation...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28130111/microrna-365-accelerates-cardiac-hypertrophy-by-inhibiting-autophagy-via-the-modulation-of-skp2-expression
#14
Haibo Wu, Yuncan Wang, Xuechao Wang, Ruyi Li, Deyun Yin
Evidence is emerging of a tight link between cardiomyocyte autophagy and cardiac hypertrophy (CH). Sustained exposure to stress leads CH to progress to heart failure. Several miRNAs have been described in heart failure, and miRNA-based therapeutic approaches are being pursued. Although microRNA-365 (miR-365) has been testified as a positive modulator of CH, the specific mechanism remains unclear. In the present study, we observed that miR-365 expression was up-regulated in hypertrophic cardiomyocytes both in vivo and in vitro, and was accompanied by dysregulation of autophagy...
January 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28120277/protein-quality-control-dysfunction-in-cardiovascular-complications-induced-by-anti-cancer-drugs
#15
Hai Ying Fu, Mikio Mukai, Nobuhisa Awata, Yasushi Sakata, Masatsugu Hori, Tetsuo Minamino
Cardiovascular complications, including heart failure, hypertension, ischemic syndromes and venous thromboembolism, have been identified in patients treated with anti-cancer drugs. Oxidative stress, mitochondrial dysfunction and DNA synthesis inhibition are considered to be responsible for the cardiotoxicity induced by these agents. Protein quality control (PQC) has 3 major components, including the endoplasmic reticulum (ER), the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system, and participates in protein folding and degradation to maintain protein homeostasis...
January 24, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28118075/dietary-spermidine-for-lowering-high-blood-pressure
#16
Tobias Eisenberg, Mahmoud Abdellatif, Andreas Zimmermann, Sabrina Schroeder, Tobias Pendl, Alexandra Harger, Slaven Stekovic, Julia Schipke, Christoph Magnes, Albrecht Schmidt, Christoph Ruckenstuhl, Christopher Dammbrueck, Angelina S Gross, Viktoria Herbst, Didac Carmona-Gutierrez, Federico Pietrocola, Thomas R Pieber, Stephan J Sigrist, Wolfgang A Linke, Christian Mühlfeld, Junichi Sadoshima, Joern Dengjel, Stefan Kiechl, Guido Kroemer, Simon Sedej, Frank Madeo
Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure...
January 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28108421/tlr4-knockout-attenuated-high-fat-diet-induced-cardiac-dysfunction-via-nf-%C3%AE%C2%BAb-jnk-dependent-activation-of-autophagy
#17
Nan Hu, Yingmei Zhang
Obesity is commonly associated with a low grade systemic inflammation, which may contribute to the onset and development of myocardial remodeling and contractile dysfunction. Toll-like receptor 4 (TLR4) plays an important role in innate immunity and inflammation although its role in high fat diet-induced obesity cardiac dysfunction remains elusive. This study was designed to examine the effect of TLR4 ablation on high fat diet intake-induced cardiac anomalies, if any, and underlying mechanism(s) involved. Wild-type (WT) and TLR4 knockout mice were fed normal or high fat (60% calorie from fat) diet for 12weeks prior to assessment of mechanical and intracellular Ca(2+) properties...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28079007/novel-therapies-targeting-cardioprotection-and-regeneration
#18
Valeria Garrido, Evelyn Mendoza-Torres, Jaime A Riquelme, Ariel Díaz, Marcela Pizarro, Mario Bustamante, Myra N Chavez, María Paz Ocaranza, Rosemarie Mellado, Ramon Corbalan, Miguel L Allende, Sergio Lavandero
Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy...
January 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28069395/rutin-attenuates-doxorubicin-induced-cardiotoxicity-via-regulating-autophagy-and-apoptosis
#19
Yanyan Ma, Lifang Yang, Jipeng Ma, Linhe Lu, Xiaowu Wang, Jun Ren, Jian Yang
Doxorubicin as anticancer agent can cause dose-dependent cardiotoxicity and heart failure in the long term. Rutin as a polyphenolic flavonoid has been illustrated to protect hearts from diverse cardiovascular diseases. Its function is known to be related to its antioxidant and antiinflammatory activity which may regulate multiple cellular signal pathways. However, the role of rutin on doxorubicin-induced cardiotoxicity has yet to be discovered. In this study, we explored the protective role of rutin on doxorubicin-induced heart failure and elucidated the potential mechanisms of protective effects of rutin against cardiomyocyte death...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28052027/estrogen-receptor-%C3%AE-ligation-inhibits-hodgkin-lymphoma-growth-by-inducing-autophagy
#20
Marina Pierdominici, Angela Maselli, Silvia L Locatelli, Laura Ciarlo, Giuseppa Careddu, Mario Patrizio, Barbara Ascione, Antonella Tinari, Carmelo Carlo-Stella, Walter Malorni, Paola Matarrese, Elena Ortona
Although Hodgkin lymphoma (HL) is curable with current therapy, at least 20% of patients relapse or fail to make complete remission. In addition, patients who achieve long-term disease-free survival frequently undergo infertility, secondary malignancies, and cardiac failure, which are related to chemotherapeutic agents and radiation therapies. Hence, new therapeutic strategies able to counteract the HL disease in this important patient population are still a matter of study. Estrogens, in particular 17β-estradiol (E2), have been suggested to play a role in lymphoma cell homeostasis by estrogen receptors (ER) β activation...
January 31, 2017: Oncotarget
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