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iNOS cardiomyocyte

Paulo Lizano, Eman Rashed, Shaunrick Stoll, Ning Zhou, Hairuo Wen, Tristan T Hays, Gangjian Qin, Lai-Hua Xie, Christophe Depre, Hongyu Qiu
The valosin-containing protein (VCP) participates in signaling pathways essential for cell homeostasis in multiple tissues, however, its function in the heart in vivo remains unknown. Here we offer the first description of the expression, function and mechanism of action of VCP in the mammalian heart in vivo in both normal and stress conditions. By using a transgenic (TG) mouse with cardiac-specific overexpression (3.5-fold) of VCP, we demonstrate that VCP is a new and powerful mediator of cardiac protection against cell death in vivo, as evidenced by a 50% reduction of infarct size after ischemia/reperfusion versus wild type...
April 20, 2017: Scientific Reports
Justin R Kingery, Tariq Hamid, Robert K Lewis, Mohamed Ameen Ismahil, Shyam S Bansal, Gregg Rokosh, Tim M Townes, Suzanne T Ildstad, Steven P Jones, Sumanth D Prabhu
In the failing heart, iNOS is expressed by both macrophages and cardiomyocytes. We hypothesized that inflammatory cell-localized iNOS exacerbates left ventricular (LV) remodeling. Wild-type (WT) C57BL/6 mice underwent total body irradiation and reconstitution with bone marrow from iNOS(-/-) mice (iNOS(-/-)c) or WT mice (WTc). Chimeric mice underwent coronary ligation to induce large infarction and ischemic heart failure (HF), or sham surgery. After 28 days, as compared with WTc sham mice, WTc HF mice exhibited significant (p < 0...
March 2017: Basic Research in Cardiology
Mona G Amer, Nader M Mohamed, Aly A M Shaalan
Intrauterine growth restriction (IUGR) has been linked to heart disease in adulthood. This study aimed to examine the effect of gestational protein restriction during fetal and early postnatal life on the cardiac muscle structure and function in adult offspring. Pregnant female rats were randomly divided into two dietary groups: normal-protein diet (NP) and low-protein diet (LP). Fifteen male offspring from each group were included in the study. Offspring body weights were recorded at birth and monthly from weaning until 24 weeks of age while systolic blood pressure was measured weekly...
February 20, 2017: Histology and Histopathology
Gauri Akolkar, Ashim K Bagchi, Prathapan Ayyappan, Davinder S Jassal, Pawan K Singal
An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox) -induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of Vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms and nitrosative stress as well as cytokines TNFα and IL-10 in isolated cardiomyocytes...
January 18, 2017: American Journal of Physiology. Cell Physiology
Seyyedeh Elaheh Mousavi, Seyed Mahdi Rezayat, Maliheh Nobakht, Seyed Soheil Saeedi Saravi, Iraj Yazdani, Amir Rashidian, Ahmad Reza Dehpour
OBJECTIVES: An increase in nitric oxide (NO) production has been reported in cirrhotic cardiomyopathy and, portal hypertension. Since minocycline has been shown to inhibit NO overproduction, we aimed to examine its role in a rat model of CCl4-induced cirrhotic cardiovascular complications. MATERIALS AND METHODS: Portal pressure and inotropic responsiveness of isolated papillary muscles to isoproterenol were measured in cirrhotic rats, following minocycline (50 mg/kg/day for 8 weeks) treatment...
November 2016: Iranian Journal of Basic Medical Sciences
Zheng-Yi Zhang, Yi Li, Rui Li, An-An Zhang, Bo Shang, Jing Yu, Xiao-Dong Xie
BACKGROUND: Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOSs) for the synthesis of nitric oxide (NO). BH4 therapy can reverse the disease-related redox disequilibrium observed with BH4 deficiency. However, whether BH4 exerts a protective effect against radiation-induced damage to cardiomyocytes remains unknown. METHODS: Clonogenic assays were performed to determine the effects of X-ray on H9c2 cells with or without BH4 treatment...
November 20, 2016: Chinese Medical Journal
Lei Pang, Yin Cai, Eva Hoi Ching Tang, Dan Yan, Ramoji Kosuru, Haobo Li, Michael G Irwin, Haichun Ma, Zhengyuan Xia
The present study explored the potential causal link between ischemia-driven cyclooxygenase-2 (COX-2) expression and enhanced apoptosis during myocardial ischemia/reperfusion (I/R) by using H9C2 cardiomyocytes and primary rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The results showed that H/R resulted in higher COX-2 expression than that of controls, which was prevented by pretreatment with Helenalin (NFκB specific inhibitor). Furthermore, pretreatment with NS398 (COX-2 specific inhibitor) significantly attenuated H/R-induced cell injury [lower lactate dehydrogenase (LDH) leakage and enhanced cell viability] and apoptosis (higher Bcl2 expression and lower level of cleaved caspases-3 and TUNEL-positive cells) in cardiomyocytes...
2016: Oxidative Medicine and Cellular Longevity
Benjamin G Sykes, Peter M Van Steyn, Jonathan D Vignali, John Winalski, Julie Lozier, Wade E Bell, James E Turner
It has been known that both estrogen (E2) and nitric oxide (NO) are critical for proper cardiovascular system (CVS) function. It has also been demonstrated that E2 acts as an upstream effector in the nitric oxide (NO) pathway. Results from this study indicate that the use of a nitric oxide synthase (NOS) inhibitor (NOSI) which targets specifically neuronal NOS (nNOS or NOS1), proadifen hydrochloride, caused a significant depression of fish heart rates (HR) accompanied by increased arrhythmic behavior. However, none of these phenotypes were evident with either the inhibition of endothelial NOS (eNOS) or inducible NOS (iNOS) isoforms...
October 26, 2016: Brain Sciences
Aly Mohamed Ahmed
The left ventricular hypertrophy (LVH) occurs in response to the hemodynamic overload in some physiological and pathological conditions. This study was designed to investigate the possible cardioprotective effect of simvastatin (SIM) treatment against isoproterenol (ISO)-induced LVH and the probable underlying mechanism in adult male Wistar rats. Animals were allocated into 4 groups. Rats of control group received normal saline orally for 30 days and intraperitoneally for the last 7 days. Rats of SIM group received SIM orally (10 mg/kg/day in saline) for 30 days...
September 26, 2016: Folia Morphologica (Warsz)
Ernestina M De Francesco, Carmine Rocca, Francesco Scavello, Daniela Amelio, Teresa Pasqua, Damiano C Rigiracciolo, Andrea Scarpelli, Silvia Avino, Francesca Cirillo, Nicola Amodio, Maria C Cerra, Marcello Maggiolini, Tommaso Angelone
The use of Doxorubicin (Dox), a frontline drug for many cancers, is often complicated by dose-limiting cardiotoxicity in approximately 20% of patients. The G-protein estrogen receptor GPER/GPR30 mediates estrogen action as the cardioprotection under certain stressful conditions. For instance, GPER activation by the selective agonist G-1 reduced myocardial inflammation, improved immunosuppression, triggered pro-survival signaling cascades, improved myocardial mechanical performance, and reduced infarct size after ischemia/reperfusion (I/R) injury...
July 2017: Journal of Cellular Physiology
Sheng-An Su, Du Yang, Wei Zhu, Zhejun Cai, Na Zhang, Lina Zhao, Jian-An Wang, Meixiang Xiang
Interleukin-17A, a pro-inflammatory cytokine, has a direct proapoptotic effect on cardiomyocytes. However, the specific mechanism has not been clarified. In the present study, an in-vitro model of cardiomyocyte apoptosis induced by IL-17A stimulation was employed and the roles of iNOS and Stat3 involved were investigated. Our data showed that the neonatal mouse cardiomyocytes express IL-17 receptors: IL-17RA and IL-17RC, but did not express IL-17A. Exogenous IL-17A significantly induces iNOS expression and hence the cardiomyocyte apoptosis...
November 2016: Biochimica et Biophysica Acta
Britta Mayer, Josefin Soppert, Sandra Kraemer, Sabrina Schemmel, Christian Beckers, Christian Bleilevens, Rolf Rossaint, Mark Coburn, Andreas Goetzenich, Christian Stoppe
Increasing evidence indicates that argon has organoprotective properties. So far, the underlying mechanisms remain poorly understood. Therefore, we investigated the effect of argon preconditioning in cardiomyocytes within the first and second window of preconditioning. Primary isolated cardiomyocytes from neonatal rats were subjected to 50% argon for 1 h, and subsequently exposed to a sublethal dosage of hypoxia (<1% O₂) for 5 h either within the first (0-3 h) or second window (24-48 h) of preconditioning...
July 19, 2016: International Journal of Molecular Sciences
Chien-Hung Lin, Chung-Ching Lin
Glucagon-like peptide-1 (GLP-1) and GLP-1 receptors (GLP-1Rs) are responsible for glucose homeostasis, and have been shown to reduce inflammation in preclinical studies. The aim of the present study was to determine whether sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), as a GLP-1 receptor agonist, exerts an anti-inflammatory effect on cardiomyoblasts during lipopolysaccharide (LPS) stimulation. Exposure to LPS increased the expression levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and IL-1β in H9c2 cells, and also resulted in elevations in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB) nuclear translocation...
June 2016: Experimental and Therapeutic Medicine
Xueli Li, Wenliang Li, Zhonghong Gao, Hailing Li
The role of iron in the etiology of diabetes complications is not well established. Thus, this study was performed to test whether the iron-induced increase of oxidative/nitrative damage is involved in SERCA2a-related diabetic heart complication. Four randomly divided groups of rats were used: normal control group; iron overload group; diabetes group, and diabetic plus iron overload group. Iron supplementation stimulated cardiomyocyte hypertrophy and led to an increase in cardiac protein carbonyls, nitrotyrosine (3-NT) formation, and iNOS protein expression, thus resulting in abnormal myocardium calcium homeostasis of diabetic rats...
August 2016: Biochimie
Wei-Dong Qin, Guo-Liang Liu, Juan Wang, Hao Wang, Jian-Ning Zhang, Fan Zhang, Yang Ma, Xin-Ying Ji, Chen Li, Ming-Xiang Zhang
Diabetic cardiomyopathy (DCM) is characterized by structural alterations such as cardiomyocyte hypertrophy, necrosis and focal fibrosis. Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme which can be activated by DNA damage and plays a critical role in various diseases. We hypothesized that PARP-1 may play an important role in DCM and that its inhibition may protect cardiomyocytes from inflammation and apoptosis in DCM. H9c2 cardiomyocytes were treated with normal glucose, mannitol or high glucose (HG)...
June 14, 2016: Oncotarget
Hiroki Takanari, Keiko Miwa, XianMing Fu, Junichi Nakai, Akira Ito, Kousuke Ino, Hiroyuki Honda, Wataru Tonomura, Satoshi Konishi, Tobias Opthof, Marcel Ag van der Heyden, Itsuo Kodama, Jong-Kook Lee
Skeletal myoblast (SkMB) transplantation has been conducted as a therapeutic strategy for severe heart failure. However, arrhythmogenicity following transplantation remains unsolved. We developed an in vitro model of myoblast transplantation with "patterned" or "randomly-mixed" co-culture of SkMBs and cardiomyocytes enabling subsequent electrophysiological, and arrhythmogenic evaluation. SkMBs were magnetically labeled with magnetite nanoparticles and co-cultured with neonatal rat ventricular myocytes (NRVMs) on multi-electrode arrays...
October 2016: Journal of Cellular Physiology
E V Navolotskaya
The data on the properties and mechanism of action of the peptide octarphin (TPLVTLFK, the fragment 12-19 of β-endorphin)--a selective agonist of nonopioid (insensitive to the action of the opioid antagonist naloxone) β-endorphin receptor found on n immune cells (peritoneal macrophages, T and B lymphocytes of spleen and blood), endocrine (adrenal cortex, hypothalamus), cardiovascular (cardiomyocytes) systems are analyzed and systematized. Binding to the receptor octarphin increases increases the mitogen-induced pro- liferation of human and mouse T and B lymphocytes in vitro, activates murine peritoneal macrophages in vitro and in vivo, stimulates growth of human T-lymphoblast cell lines Jurkat and MT-4, inhibits adenylate cyclase activity of rat adrenal cortex membranes and suppresses the secretion of glucocorticoids from the adrenal gland into the blood...
September 2015: Bioorganicheskaia Khimiia
Qun Shao, Heng-Jie Cheng, Michael F Callahan, Dalane W Kitzman, Wei-Min Li, Che Ping Cheng
BACKGROUND: Altered nitric oxide synthase (NOS) has been implicated in the pathophysiology of heart failure (HF). Recent evidence links hypothyroidism to the pathology of HF. However, the precise mechanisms are incompletely understood. The alterations and functional effects of cardiac NOS in hypothyroidism are unknown. We tested the hypothesis that hypothyroidism increases cardiomyocyte inducible NOS (iNOS) expression, which plays an important role in hypothyroidism-induced depression of cardiomyocyte contractile properties, [Ca(2+)]i transient ([Ca(2+)]iT), and β-adrenergic hyporesponsiveness...
February 1, 2016: International Journal of Cardiology
Udesh Dhawan, Chia Hui Lee, Chun-Chung Huang, Ying Hao Chu, Guewha S Huang, Yan-Ren Lin, Wen-Liang Chen
BACKGROUND: Nitric oxide (NO) plays a very important role in the cardiovascular system as a major secondary messenger in signaling pathway. Its concentration regulates most of the important physiological indexes including the systemic blood pressure, blood flow, regional vascular tone and other cardiac functions. The effect of nanotopography on the NO secretion in cardiomyocytes has not been elucidated before. In this study, we report how the nanotopography can modulate the secretion profile of NO and attempt to elucidate the genetic pathways responsible for the same by using Tantalum Oxide nanodot arrays ranging from 10 to 200 nm...
2015: Journal of Nanobiotechnology
Muneyoshi Okada, Hideyuki Yamawaki
Levosimendan, a calcium sensitizer, known as an inotropic agent has a cytoprotective effect against apoptosis in cardiomyocytes. However, the cytoprotective effect of levosimendan on cardiac fibroblasts has not been clarified. The aim of this study was to examine whether levosimendan modulates interleukin (IL)-1β-induced apoptosis in adult rat cardiac fibroblast. Cardiac fibroblasts were isolated from adult male Wistar rats. Apoptosis of cardiac fibroblasts was evaluated by 4',6-diamidino-2-phenylindole staining and TdT-mediated d-UTP nick end labeling (TUNEL)-based staining...
December 15, 2015: European Journal of Pharmacology
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