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Reversing heart disease

Oscar H L Bing
Ammonia plays a central role in the life and death of all living organisms and has been studied for over one hundred years. Ammonia is necessary for growth and development but it is toxic in excess and, as a result, differing methods of ammonia neutralization have evolved. Following physiological and pathological stress to the heart, tissue ammonia levels rise. Local ammonia neutralization may be inadequate and excess ammonia may exert its toxic effects. Phenylbutyrate (PBA), which is FDA approved for the treatment of elevated blood ammonia in urea cycle disorders, provides an accessory pathway for ammonia clearance...
March 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Faisal Junejo, Mohammad Irfan Akhtar, Mohammad Hamid, Syed Shabbir Ahmed, Fauzia Minai, Muneer Amanullah
OBJECTIVE: To compare the intravenous boluses and intravenous continuous infusion of tranexamic acid (TXA) to reduce postoperative bleeding in cyanotic congenital heart disease surgeries. STUDY DESIGN: Single-blinded randomised clinical trial. PLACE AND DURATION OF STUDY: Anaesthesia Department, The Aga Khan University Hospital, Karachi, from July 2016 to April 2017. METHODOLOGY: Sixty patients of cyanotic congenital heart disease, undergoing either palliative or corrective surgery involving cardiopulmonary bypass (CPB), were recruited...
March 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Fang Qiu, Changjiang Dong, Yanxin Liu, Xiaoqi Shao, Di Huang, Yanna Han, Bing Wang, Yanli Liu, Rong Huo, Petro Paulo, Zhiren Zhang, Dan Zhao, Wen-Feng Chu
BACKGROUND AND PURPOSE: Protein modification by small ubiquitin-like modifier (SUMO) plays a critical role in the pathogenesis of heart diseases. The present study was designed to determine whether ginkgolic acid (GA) as a SUMO-1 inhibitor exerts an inhibitory effect on cardiac fibrosis induced by myocardial infarction (MI). EXPERIMENTAL APPROACH: GA was delivered by osmotic pumps in MI mice. Masson staining, electron microscopy (EM) and echocardiography were used to assess cardiac fibrosis, ultrastructure and function...
March 7, 2018: Toxicology and Applied Pharmacology
Wei Lei, Tingting Feng, Xing Fang, You Yu, Junjie Yang, Zhen-Ao Zhao, Junwei Liu, Zhenya Shen, Wenbo Deng, Shijun Hu
BACKGROUND: Circular RNAs (circRNAs) are regarded as a novel class of noncoding RNA regulators. Although a number of circRNAs have been identified by bioinformatics analysis of RNA-seq data, tissue and disease-specific circRNAs are still to be uncovered to promote their application in basic research and clinical practice. The purpose of this study was to explore the circRNA profiles in human induced pluripotent stem cells (hiPSCs) and hiPSC-derived cardiomyocytes (hiPSC-CMs), and to identify cardiac or disease-specific circRNAs...
March 9, 2018: Stem Cell Research & Therapy
Xuelian Li, GuoYuan Wang, MuGe QiLi, HaiHai Liang, TianShi Li, XiaoQiang E, Ying Feng, Ying Zhang, Xiao Liu, Ming Qian, BoZhi Xu, ZhiHang Shen, Samuel Chege Gitau, DanDan Zhao, HongLi Shan
BACKGROUND/AIMS: Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment...
March 2, 2018: Cellular Physiology and Biochemistry
Yanjiao Li, Li Li, Zhengjiang Qian, Boya Lin, Jidong Chen, Yixuan Luo, Junle Qu, J Usha Raj, Deming Gou
BACKGROUND: Platelet-derived growth factor BB, a potent mitogen of pulmonary artery smooth muscle cells (PASMCs), has been implicated in pulmonary arterial remodeling, which is a key pathogenic feature of pulmonary arterial hypertension. Previous microRNA profiling in platelet-derived growth factor BB-treated PASMCs found a significantly downregulated microRNA, miR-1281, but it has not been associated with any cellular function, and we investigated the possibility. METHODS AND RESULTS: Real-time quantitative reverse transcription-polymerase chain reaction assay proved that downregulation of miR-1281 was a conserved phenomenon in human and rat PASMCs...
March 7, 2018: Journal of the American Heart Association
Barbara Ogórek, Hilaire C Lam, Damir Khabibullin, Heng-Jia Liu, Julie Nijmeh, Robinson Triboulet, David J Kwiatkowski, Richard I Gregory, Elizabeth P Henske
Tuberous Sclerosis Complex (TSC) is an autosomal dominant disease caused by germline inactivating mutations of TSC1 or TSC2. In TSC-associated tumors of the brain, heart, skin, kidney, and lung, inactivation of both alleles of TSC1 or TSC2 leads to hyperactivation of the mTORC1 pathway. The TSC/mTORC1 pathway is a key regulator of cellular processes related to growth, proliferation and autophagy. We and others have previously found that mTORC1 regulates microRNA biogenesis, but the mechanisms are not fully understood...
March 2, 2018: Human Molecular Genetics
Caroline M Van De Heyning, Catherine De Maeyer, Nele Pattyn, Paul J Beckers, Véronique A Cornelissen, Kaatje Goetschalckx, Nadine Possemiers, Emeline M Van Craenenbroeck, Jens-Uwe Voigt, Luc Vanhees, Bharati Shivalkar
BACKGROUND: Increase of exercise capacity (peak VO2 ) after cardiac rehabilitation improves outcome in patients with coronary artery disease (CAD). Systolic and diastolic function have been associated with peak VO2 , but their role towards improvement of exercise capacity remains unclear. It is unknown which exercise intensity has the most beneficial impact on left ventricular (LV) geometry and function in CAD patients without heart failure. METHODS: 200 stable CAD patients without heart failure were randomized to 3months of aerobic interval training (AIT) or aerobic continuous training (ACT)...
April 15, 2018: International Journal of Cardiology
Nathan Cho, Shadi E Razipour, Megan L McCain
Cardiac fibroblasts and their activated derivatives, myofibroblasts, play a critical role in wound healing after myocardial injury and often contribute to long-term pathological outcomes, such as excessive fibrosis. Thus, defining the microenvironmental factors that regulate the phenotype of cardiac fibroblasts and myofibroblasts could lead to new therapeutic strategies. Both chemical and biomechanical cues have previously been shown to induce myofibroblast differentiation in many organs and species. For example, transforming growth factor beta 1, a cytokine secreted by neutrophils, and rigid extracellular matrix environments have both been shown to promote differentiation...
January 1, 2018: Experimental Biology and Medicine
Mika Watanabe, Masaki Izumo, Yoshihiro J Akashi
Takotsubo cardiomyopathy is described as a transient reversible cardiomyopathy which typically occurs in older women after emotional or physical stress. This cardiomyopathy is also recognized as a "syndrome" because it develops in conjunction with various diseases. Since the clinical presentation of takotsubo syndrome (TTS) is similar to acute coronary syndrome (ACS), TTS should be distinguished from ischemic heart disease. Although the pathophysiology of TTS has not well been established, a number of its specific features have been suggested...
March 5, 2018: International Heart Journal
Sarah E D Nelson, Kim N Ha, Tata Gopinath, Mara H Exline, Alessandro Mascioni, David D Thomas, Gianluigi Veglia
Approximately, 70% of the Ca2+ ion transport into the sarcoplasmic reticulum is catalyzed by the sarcoplasmic reticulum Ca2+ -ATPase (SERCA), whose activity is endogenously regulated by phospholamban (PLN). PLN comprises a TM inhibitory region and a cytoplasmic regulatory region that harbors a consensus sequence for cAMP-dependent protein kinase (PKA). The inhibitory region binds the ATPase, reducing its apparent Ca2+ binding affinity. β-adrenergic stimulation activates PKA, which phosphorylates PLN at Ser 16, reversing its inhibitory function...
March 1, 2018: Biochimica et Biophysica Acta
Yong Li, Qiu-Hua Yu, Ying Chu, Wei-Min Wu, Jian-Xiang Song, Xiao-Bo Zhu, Qiang Wang
Hypertension is a multifactorial chronic inflammatory disease that leads to cardiac remodeling. A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that has multiple functions in various biological events, including the regulation of vessel integrity and differentiation of neural barriers in blood. However, the role of AKAP12 in angiotensin II (Ang II)-induced cardiac injury remains unclear. In the present study, Ang II infusion reduced AKAP12 expressions in the hearts of wild-type (WT) mice, and AKAP12 knockout (KO) enhanced the infiltration of inflammatory cells...
February 28, 2018: Biochemical and Biophysical Research Communications
Erin J Howden, André La Gerche, Jane F Arthur, Julie R McMullen, Garry L Jennings, David W Dunstan, Neville Owen, Sharon Avery, Bronwyn A Kingwell
Hematological cancer survivors are highly vulnerable to cardiometabolic complications impacting long-term health status, quality of life and survival. Elevated risk of diabetes and cardiovascular disease arises not only from the effects of the cancers themselves, but also from the toxic effects of cancer therapies, and deconditioning arising from reduced physical activity levels. Regular physical activity can circumvent or reverse adverse effects on the heart, skeletal muscle, vasculature and blood cells, through a combination of systemic and molecular mechanisms...
February 21, 2018: Blood Reviews
Syed Rafay Ali Sabzwari, Zoltan Varga, Khurram Butt, Nimra Khan
Vasospastic angina (VSA), also known as variant or Prinzmetal's angina, is a relatively uncommon cause of retrosternal chest pain with transient ST segment elevation, mainly due to vasospasm in the coronary arteries. This is a case of 37-year-old female who presented with chest pain and syncope. Her initial workup, including echocardiogram, was negative. Subsequently, she was sent home with an event monitor. During the next two weeks, she continued to have recurrent episodes of similar chest pains and presented to her cardiology appointment with a heart rate of 45 bpm and blood pressure of 100/60 mmHg and was taken to hospital emergency department...
December 16, 2017: Curēus
Paul Wijnker, Vasco Sequeira, Diederik Kuster, Jolanda van der Velden
SIGNIFICANCE: Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by left ventricular hypertrophy, diastolic dysfunction and myocardial disarray. Disease onset occurs between 20 and 50 years of age, thus affecting patients in the prime of their life. HCM is caused by mutations in sarcomere proteins, the contractile building blocks of the heart. Despite increased knowledge of causal mutations, the exact path from genetic defect leading to cardiomyopathy is complex and involves additional disease hits...
February 28, 2018: Antioxidants & Redox Signaling
Gustavo Chavez, Ilana B Richman, Rajani Kaimal, Jason Bentley, Lee Ann Yasukawa, Russ B Altman, Vyjeyanthi S Periyakoil, Jonathan H Chen
IMPORTANCE: Critically ill patients often receive high-intensity life sustaining treatments (LST) in the intensive care unit (ICU), although they can be ineffective and eventually undesired. Determining the risk factors associated with reversals in LST goals can improve patient and provider appreciation for the natural history and epidemiology of critical care and inform decision making around the (continued) use of LSTs. METHODS: This is a single institution retrospective cohort study of patients receiving life sustaining treatment in an academic tertiary hospital from 2009 to 2013...
2018: PloS One
Lei Yang, Kaarina Korhonen, Heta Moustgaard, Karri Silventoinen, Pekka Martikainen
BACKGROUND: Previous studies have found depression to be negatively associated with the prognosis of both cardiovascular disease (CVD) and cancer, but this may partly reflect reverse causality. We limited the possibility of reverse causality by measuring depression before the first diagnosis of CVD or cancer. METHODS: We used an 11% longitudinal random sample of the Finnish population aged 25 years or older who are residents of Finland for at least 1 year between 1987 and 2007, with an 80% oversample of those who died during this period...
February 26, 2018: Journal of Epidemiology and Community Health
Li Huang, Li Li, Enci Hu, Guo Chen, Xianmin Meng, Changming Xiong, Jianguo He
No abstract text is available yet for this article.
January 1, 2018: Pulmonary Circulation
Jens M Hohlfeld, Jens Vogel-Claussen, Heike Biller, Dominik Berliner, Korbinian Berschneider, Hanns-Christian Tillmann, Simone Hiltl, Johann Bauersachs, Tobias Welte
BACKGROUND: Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA-inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. METHODS: We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic...
February 21, 2018: Lancet Respiratory Medicine
Timothy Mitchell, James W MacDonald, Sengkeo Srinouanpranchanh, Theodor K Bammler, Sean Merillat, Erica Boldenow, Michelle Coleman, Kathy Agnew, Audrey Baldessari, Jennifer E Stencel-Baerenwald, Jennifer Tisoncik-Go, Richard R Green, Michael J Gale, Lakshmi Rajagopal, Kristina M Adams Waldorf
BACKGROUND: Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. OBJECTIVE: The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development...
February 21, 2018: American Journal of Obstetrics and Gynecology
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