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Cardiac autophagy

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https://www.readbyqxmd.com/read/29452090/activation-of-calcium-sensing-receptor-mediated-autophagy-in-angiotensinii-induced-cardiac-fibrosis-in-vitro
#1
Jinyu Chi, Lei Wang, Xiaohui Zhang, Yu Fu, Yue Liu, Wenjia Chen, Wenxiu Liu, Zhiyu Shi, Xinhua Yin
Cardiac fibrosis is one of the primary mechanisms of ventricular remodeling, and there is no effective method for reversal. Activation of calcium sensing receptor (CaSR) has been reported to be involved in the development of myocardial fibrosis, but the molecular mechanism for CaSR activation has not yet been clarified and needs to be further explored. Here, we found that AngII induces cardiac fibroblast proliferation and phenotypic transformation in a dose-dependent manner with increased CaSR and autophagy related protein (Beclin1, LC3B) expression...
February 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29446053/systems-pharmacological-analysis-of-mitochondrial-cardiotoxicity-induced-by-selected-tyrosine-kinase-inhibitors
#2
Tanaya Vaidya, Jeff Kamta, Maher Chaar, Anusha Ande, Sihem Ait-Oudhia
Tyrosine kinase inhibitors (TKIs) are targeted therapies rapidly becoming favored over conventional cytotoxic chemotherapeutics. Our study investigates two FDA approved TKIs, DASATINIB; indicated for IMATINIB-refractory chronic myeloid leukemia, and SORAFENIB; indicated for hepatocellular carcinoma and advanced renal cell carcinoma. Limited but crucial evidence suggests that these agents can have cardiotoxic side effects ranging from hypertension to heart failure. A greater understanding of the underlying mechanisms of this cardiotoxicity are needed as concerns grow and the capacity to anticipate them is lacking...
February 14, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29441645/short-telomeres-induce-p53-and-autophagy-and-modulate-age-associated-changes-in-cardiac-progenitor-cell-fate
#3
Collin Matsumoto, Yan Jiang, Jacqueline Emathinger, Pearl Quijada, Nathalie Nguyen, Andrea De La Torre, Maryam Moshref, Jonathan Nguyen, Aimee B Levinson, Minyoung Shin, Mark A Sussman, Nirmala Hariharan
Aging severely limits myocardial repair and regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesized that short telomeres activate p53 and induce autophagy to elicit the age-associated change in CPC fate. We isolated CPCs and compared mouse strains with different telomere lengths for phenotypic characteristics of aging. Wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres exhibits early cardiac aging with cardiac dysfunction, hypertrophy, fibrosis and senescence, as compared to common lab strains FVB and C57 bearing longer telomeres...
February 14, 2018: Stem Cells
https://www.readbyqxmd.com/read/29427791/cyp2j2-derived-eets-attenuated-ethanol-induced-myocardial-dysfunction-through-inducing-autophagy-and-reducing-apoptosis
#4
Chi Zhou, Jin Huang, Qing Li, Chenao Zhan, Xizhen Xu, Xu Zhang, Ding Ai, Yi Zhu, Zheng Wen, Dao Wen Wang
Chronic excessive drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, where ethanol toxicity plays an essential role. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acids to form epoxyeicosatrienoic acids (EETs), which exert beneficial roles in the cardiovascular system, but their role in alcoholic cardiomyopathy is elusive. This study was designed to evaluate the effects and mechanisms of CYP2J2 gene delivery on ethanol-induced myocardial dysfunction with focus on autophagy and apoptosis...
February 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29420210/new-insights-into-the-role-of-mtor-signaling-in-the-cardiovascular-system
#5
REVIEW
Sebastiano Sciarretta, Maurizio Forte, Giacomo Frati, Junichi Sadoshima
The mTOR (mechanistic target of rapamycin) is a master regulator of several crucial cellular processes, including protein synthesis, cellular growth, proliferation, autophagy, lysosomal function, and cell metabolism. mTOR interacts with specific adaptor proteins to form 2 multiprotein complexes, called mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2). In the cardiovascular system, the mTOR pathway regulates both physiological and pathological processes in the heart. It is needed for embryonic cardiovascular development and for maintaining cardiac homeostasis in postnatal life...
February 2, 2018: Circulation Research
https://www.readbyqxmd.com/read/29416668/molecular-mechanisms-of-cardioprotective-effects-mediated-by-transplanted-cardiac-ckit-cells-through-the-activation-of-an-inflammatory-hypoxia-dependent-reparative-response
#6
Giovanni Puddighinu, Domenico D'Amario, Eleonora Foglio, Melissa Manchi, Andrea Siracusano, Elena Pontemezzo, Martina Cordella, Francesco Facchiano, Laura Pellegrini, Antonella Mangoni, Marco Tafani, Filippo Crea, Antonia Germani, Matteo Antonio Russo, Federica Limana
The regenerative effects of cardiac ckit+ stem cells (ckit+CSCs) in acute myocardial infarction (MI) have been studied extensively, but how these cells exert a protective effect on cardiomyocytes is not well known. Growing evidences suggest that in adult stem cells injury triggers inflammatory signaling pathways which control tissue repair and regeneration. Aim of the present study was to determine the mechanisms underlying the cardioprotective effects of ckit+CSCs following transplantation in a murine model of MI...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416039/bfgf-plays-a-neuroprotective-role-by-suppressing-excessive-autophagy-and-apoptosis-after-transient-global-cerebral-ischemia-in-rats
#7
Dawei Sun, Wenying Wang, Xintao Wang, Yan Wang, Xiaotao Xu, Feng Ping, Yu Du, Wei Jiang, Derong Cui
Transient global cerebral ischemia (tGCI) is a cerebrovascular disorder that can cause apoptotic neuronal damage and functional deficits. Basic fibroblast growth factor (bFGF) was reported to be highly expressed in the central nervous system (CNS) and to exert neuroprotective effects against different CNS diseases. However, the effects of bFGF on tGCI have not been studied intensively. This study was conducted to investigate the effect of bFGF and its underlying mechanism in an animal model of tGCI. After intracerebroventricular (i...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29410090/temporal-partitioning-of-adaptive-responses-of-the-murine-heart-to-fasting
#8
Rachel A Brewer, Helen E Collins, Ryan D Berry, Manoja K Brahma, Brian A Tirado, Rodrigo A Peliciari-Garcia, Haley L Stanley, Adam R Wende, Heinrich Taegtmeyer, Namakkal Soorappan Rajasekaran, Victor Darley-Usmar, Jianhua Zhang, Stuart J Frank, John C Chatham, Martin E Young
Recent studies suggest that the time of day at which food is consumed dramatically influences clinically-relevant cardiometabolic parameters (e.g., adiposity, insulin sensitivity, and cardiac function). Meal feeding benefits may be the result of daily periods of feeding and/or fasting, highlighting the need for improved understanding of the temporal adaptation of cardiometabolic tissues (e.g., heart) to fasting. Such studies may provide mechanistic insight regarding how time-of-day-dependent feeding/fasting cycles influence cardiac function...
January 30, 2018: Life Sciences
https://www.readbyqxmd.com/read/29409895/bcl-2-associated-athanogene-3-bag3-is-an-enhancer-of-small-heat-shock-protein-turnover-via-activation-of-autophagy-in-the-heart
#9
Yui Inomata, Shouta Nagasaka, Kazuki Miyate, Yuta Goto, Chizuru Hino, Chihiro Toukairin, Rieko Higashio, Kinji Ishida, Tomoyuki Saino, Masamichi Hirose, Hideki Tsumura, Atsushi Sanbe
Bcl-2-associated athanogene 3 (BAG3) is strongly expressed in both cardiac and skeletal muscle. A recent study showed that BAG3 may play a protective role in muscles. Little is known, however, regarding the detailed role of BAG3 in cardiac muscle. To better understand the functional role of cardiac BAG3 in the heart, we generated transgenic (TG) mice that overexpress BAG3. A decrease in fractional shortening, and the induction of cardiac atrial natriuretic peptide, were observed in BAG3 TG mice. Moreover, a marked reduction in the protein level of small HSPs was detected in BAG3 TG mouse hearts...
January 31, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29403560/thrombopoietin-protects-h9c2-cells-from-excessive-autophagy-and-apoptosis-in-doxorubicin-induced-cardiotoxicity
#10
Han Wang, Hua Wang, En-Yu Liang, Li-Xia Zhou, Zhan-Ling Dong, Ping Liang, Qi-Fang Weng, Mo Yang
Cardiac toxicity has been the major concern when using doxorubicin (DOX) in cancer therapy. Thrombopoietin (TPO) protects cardiac cells from DOX-induced cell damage; however, its molecular mechanism remains exclusive. The anti-autophagic and anti-apoptotic effects of TPO upon DOX treatment were studied in the cardiac H9C2 cell line, with bafilomycin A1 treatment as a positive control for autophagy inhibition. Cell viability was measured by Cell Counting Kit-8 assay in different treatment groups. The mRNA and/or protein levels of apoptotic markers and autophagy-associated factors were detected...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29402990/diastolic-dysfunction-is-more-apparent-in-stz-induced-diabetic-female-mice-despite-less-pronounced-hyperglycemia
#11
Chanchal Chandramouli, Melissa E Reichelt, Claire L Curl, Upasna Varma, Laura A Bienvenu, Parisa Koutsifeli, Antonia J A Raaijmakers, Miles J De Blasio, Cheng Xue Qin, Alicia J Jenkins, Rebecca H Ritchie, Kimberley M Mellor, Lea M D Delbridge
Diabetic cardiomyopathy is a distinct pathology characterized by early emergence of diastolic dysfunction. Increased cardiovascular risk associated with diabetes is more marked for women, but an understanding of the role of diastolic dysfunction in female susceptibility to diabetic cardiomyopathy is lacking. To investigate the sex-specific relationship between systemic diabetic status and in vivo occurrence of diastolic dysfunction, diabetes was induced in male and female mice by streptozotocin (5x daily i...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29402364/-role-of-microrna-1-mediated-amp-activated-protein-kinase-pathway-in-cardiac-fibroblasts-induced-by-high-glucose-in-rats
#12
Jia Qiu, An Wang, Yingna Xu, Shigang Qiao, Jianzhong An, Hua Li, Chen Wang
OBJECTIVE: To investigate the role of microRNA-1 (miR-1) in cardiac fibroblasts induced by high glucose in rats. METHODS: The primary fibroblasts were cultured from the apical tissue of 1-3 day-old Sprague-Dawley (SD) rats. The cells which were passaged to generation 3 or 4, were randomly divided into normal glucose+lentivector-vehicle group (CON+Lv-Vehicle group), normal glucose+lentivector-miR-1 group (CON+Lv-miR1 group), high glucose+lentivector-vehicle group (HG+Lv-Vehicle group), high glucose+lentivector-miR-1 group (HG+Lv-miR1 group), high glucose+Lv-Vehicle+inhibitor group (HG+Lv-Vehicle+CC group), and high glucose+lentivector-miR-1+inhibitor group (HG+Lv-miR1+CC group)...
February 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/29391491/mir-26a-5p-regulates-cardiac-fibroblasts-collagen-expression-by-targeting-ulk1
#13
Liling Zheng, Sihuang Lin, Chengyu Lv
MiRNA is a class of small non-coding RNA which has an important effect on posttranscriptional gene regulation. It can regulate the expression of the target gene at the mRNA level and further influence the protein level of the target gene. We found that ULK1 may be the target gene of miR-26a-5p, and ULK1 (unc-51 like autophagy activating kinase 1) is a key component in autophagy pathway. In this study, we overexpressed miR-26a-5p by transfecting miR-26a-5p mimic into cells and simultaneously inhibited miR-26a-5p by transfecting miR-26a-5p inhibitor into cells...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29388469/akap1-genetic-deletion-increases-the-severity-of-hyperoxia-induced-acute-lung-injury-in-mice
#14
Venkata R Narala, Jutaro Fukumoto, Helena Hernández-Cuervo, Sahebgowda Sidramagowda Patil, Sudarshan Krishnamurthy, Mason Breitzig, Lakshmi Galam, Ramani Soundararajan, Richard F Lockey, Narasaiah Kolliputi
Critically ill patients are commonly treated with high levels of oxygen, hyperoxia, for prolonged periods of time. Unfortunately, extended exposure to hyperoxia can exacerbate respiratory failure and lead to a high mortality rate. Mitochondrial A-kinase anchoring protein (Akap) has been shown to regulate mitochondrial function. It has been reported that, under hypoxic conditions, Akap121 undergoes proteolytic degradation and promotes cardiac injury. However, the role of Akap1 in hyperoxia-induced acute lung injury (ALI) is largely unknown...
February 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29374920/-autophagy-and-hypoxic-ischemic-myocardial-damage-after-severe-burn
#15
Y S Huang
It is an important clinical subject to illuminate the mechanisms of myocardial damage in the early stage post severe burn in prevention against and treatment of burn shock, which may offer a targeted " dynamic support" in the treatment of severe burn patients. In recent years, the role of autophagy in hypoxic myocardial injury has attracted much attention. Autophagy is a physiological phenomenon on intracellular digestion process of long-life proteins and the aging and damaged organelles through lysosomal system, and it is essential for maintaining the homeostasis of cells...
January 20, 2018: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29351515/understanding-key-mechanisms-of-exercise-induced-cardiac-protection-to-mitigate-disease-current-knowledge-and-emerging-concepts
#16
Bianca C Bernardo, Jenny Y Y Ooi, Kate L Weeks, Natalie L Patterson, Julie R McMullen
The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#17
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29345251/cancer-associated-cachexia
#18
REVIEW
Vickie E Baracos, Lisa Martin, Murray Korc, Denis C Guttridge, Kenneth C H Fearon
Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy expenditure, excess catabolism and inflammation. Cachexia is highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel; this group of malignancies is responsible for half of all cancer deaths worldwide. Cachexia involves diverse mediators derived from the cancer cells and cells within the tumour microenvironment, including inflammatory and immune cells...
January 18, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29344913/cardiac-basal-autophagic-activity-and-increased-exercise-capacity
#19
Fang-Hui Li, Tao Li, Ying-Min Su, Jing-Yi Ai, Rui Duan, Timon Cheng-Yi Liu
To investigate whether high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) have different impacts on exercise performance and cardiac function and to determine the influence of these exercise protocols on modulating basal autophagy in the cardiac muscle of rats. Rats were assigned to three groups: sedentary control (SC), CMT, and HIIT. Total exercise volume and mean intensity were matched between the two protocols. After a 10-week training program, rats were evaluated for exercise performance, including exercise tolerance and grip strength...
January 17, 2018: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/29335450/copper-sulfide-nanoparticles-as-a-photothermal-switch-for-trpv1-signaling-to-attenuate-atherosclerosis
#20
Wen Gao, Yuhui Sun, Michelle Cai, Yujie Zhao, Wenhua Cao, Zhenhua Liu, Guanwei Cui, Bo Tang
Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx...
January 15, 2018: Nature Communications
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