Muscle Cell News Volume 4.15 | Apr 29 2019

TOP STORY

Chronic Hypoxia-Induced Cirbp Hypermethylation Attenuates Hypothermic Cardioprotection via Down-Regulation of Ubiquinone Biosynthesis

The authors tested whether chronic hypoxia (CH) attenuated hypothermic cardioprotection during cardiopulmonary bypass (CPB). Using a rat model of CPB, they found that hypothermic cardioprotection was impaired in CH rats but was preserved in normoxic rats. Cardiac proteomes showed that cold-inducible RNA binding protein was significantly decreased in CH rats during CPB. [Sci Transl Med] Abstract

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Pioneering Function of Isl1 in the Epigenetic Control of Cardiomyocyte Cell Fate

Researchers showed that Isl1 acted as a pioneer factor driving cardiomyocyte lineage commitment by shaping the chromatin landscape of cardiac progenitor cells. Using an Isl1 hypomorphic mouse line which showed congenital heart defects, genome-wide profiling of Isl1 binding together with RNA- and ATAC-sequencing of cardiac progenitor cells and their derivatives, they uncovered a regulatory network downstream of Isl1 that orchestrated cardiogenesis. [Cell Res] Full Article

Ibrutinib Displays Atrial-Specific Toxicity in Human Stem Cell-Derived Cardiomyocytes

Scientists employed cell-specific differentiation protocols and optical mapping to investigate the effects of ibrutinib (IB) and other tyrosine kinase inhibitors on the voltage and calcium transients of atrial and ventricular human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). IB demonstrated direct cell-specific effects on atrial hPSC-CMs that would be predicted to predispose to atrial fibrillation. [Stem Cell Reports] Full Article

The Transmembrane Protein Crb2a Regulates Cardiomyocyte Apicobasal Polarity and Adhesion in Zebrafish

Investigators showed that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, displayed compacted wall integrity defects and fail to form trabeculae. Crb2a localization was very dynamic at a time when other cardiomyocyte junctional proteins also relocalized. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a was expressed in all ventricular cardiomyocytes and colocalized with the junctional protein ZO-1. [Development] Abstract | Press Release

Insulin-Dependent GLUT4 Trafficking Is Not Regulated by Protein SUMOylation in L6 Myocytes

Several lines of evidence have implicated the post-translational modification, SUMOylation, in insulin signalling and insulin resistance in skeletal muscle. The authors examined this possibility by manipulation of cellular SUMOylation levels using multiple different tools, and assaying the effect on insulin-stimulated GLUT4 surface expression in differentiated L6 rat myocytes. [Sci Rep] Full Article

SKELETAL MUSCLE CELLS

Myonuclear Accretion Is a Determinant of Exercise-Induced Remodeling in Skeletal Muscle

Scientists developed a high-intensity interval training (HIIT) protocol and assessed the importance of muscle progenitors (MP) fusion. In eight month-old mice, HIIT led to progressive myonuclear accretion throughout the protocol, and functional muscle hypertrophy. Abrogation of MP fusion at the onset of HIIT resulted in exercise intolerance and fibrosis. [eLife] Abstract

Lactate Stimulates a Potential for Hypertrophy and Regeneration of Mouse Skeletal Muscle

Oral lactate administration increased the muscle weight and fiber cross-sectional area, and the population of Pax7-positive nuclei in mouse tibialis anterior (TA) skeletal muscle. Oral administration of lactate also facilitated the recovery process of cardio toxin-associated injured mouse TA muscle mass accompanied with a transient increase in the population of Pax7-positive nuclei. [Nutrients] Full Article

miR-34b-5p Mediates the Proliferation and Differentiation of Myoblasts by Targeting IGFBP2

Dual-luciferase reporter assay and Western blot analysis showed that IGFBP2 is a direct target of miR-34b-5p. Flow cytometric analysis and EdU assay showed that miR-34b-5p could repress the cell cycle progression of myoblasts, and miR-34b-5p could promote the formation of myotubes by promoting the expression of MyHC. [Cells] Full Article

SMOOTH MUSCLE CELLS

Differing Calcification Processes in Cultured Vascular Smooth Muscle Cells and Osteoblasts

Investigators used primary mouse vascular smooth muscle cells (VSMs) and calvarial osteoblasts to directly compare the established and widely used in vitro models of arterial medial calcification and bone formation. Significant differences were identified between osteoblasts and calcifying VSMCs. [Exp Cell Res] Full Article

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Molecular Mechanisms of Arrhythmogenic Cardiomyopathy

Through the development of animal, induced pluripotent stem cell and other models of disease, advances in the understanding of the pathogenic mechanisms of arrhythmogenic cardiomyopathy over the past decade have brought several signaling pathways into focus. These pathways include canonical and non-canonical WNT signaling, the Hippo-Yes-associated protein pathway and transforming growth factor-β signaling. [Nat Rev Cardiol] Abstract

Pericytes: Key Players in Spinal Cord Injury

The arising knowledge from current research will contribute to novel approaches to develop therapies for spinal cord injury. Here, investigators review novel advances in the understanding of pericyte biology in the spinal cord. [Am J Pathol] Abstract

Visit our reviews page to see a complete list of reviews in the muscle cell research field.

Orphazyme’s Phase II/III Trial in Sporadic Inclusion Body Myositis Fully Enrolled

Orphazyme A/S announced that its Phase II/III trial of arimoclomol for the treatment of sporadic inclusion body myositis is fully enrolled. Performance of interim analysis and study completion expected in H1 2020 and by end 2020, respectively. [Orphazyme A/S] Press Release

ARCA Biopharma Announces Steering Committee of Leading International Cardiology and Electrophysiology Experts for PRECISION-AF Phase III Clinical Trial

ARCA Biopharma, Inc. announced the initial members of the Steering Committee for PRECISION-AF, the company’s planned Phase III trial evaluating Gencaro™ as potentially the first genetically-targeted treatment for atrial fibrillation. [ARCA Biopharma] Press Release

FDA Approves Praluent^® (Alirocumab) to Prevent Heart Attack, Stroke and Unstable Angina Requiring Hospitalization

The FDA has approved Praluent^® to reduce the risk of heart attack, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. [Sanofi (GlobeNewswire, Inc.)] Press Release

Fulcrum Therapeutics Acquires Global Rights to Losmapimod, a Potential Disease-Modifying Therapy for Facioscapulohumeral Muscular Dystrophy

Fulcrum Therapeutics announced an exclusive worldwide license agreement with GlaxoSmithKline for development and commercialization of the investigational drug losmapimod. Fulcrum intends to advance losmapimod into a Phase IIb trial in the rare and devastating genetic disease facioscapulohumeral muscular dystrophy, for which there are currently no approved treatments. [Fulcrum Therapeutics] Press Release

Novartis Unveils Investigation of Infant’s Death in European Zolgensma Trial

Novartis is digging into the death of an infant, reported by FiercePharma last Wednesday, who was treated as part of Zolgensma’s ongoing European Phase III trial. Zolgensma, a one-time therapy targeting spinal muscular atrophy Type 1 with a prospective price tag of up to $5 million, is poised for an FDA decision next month. [Questex LLC] Press Release

US Universities Reassess Collaborations with Foreign Scientists in Wake of NIH Letters

Kuspa’s attempt to stay ahead of NIH came to naught. A few months into the audit, Baylor College of Medicine received letters from the US National Institutes of Health (NIH) asking about four scientists it believed had violated the agency’s rule requiring them to disclose all foreign ties relating to their research. [ScienceInsider] Editorial

Elsevier and Norway Agree on New Open-Access Deal

After unsuccessful negotiations between a coalition of Norwegian organizations and the academic publisher Elsevier culminated in canceled subscriptions earlier this year, the two have successfully established a new nationwide licensing agreement. [The Scientist] Editorial

NEW Structural Heart Summit
June 12-15, 2019
Chicago, Illinois, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Cardiovascular Epidemiology (Boston University School of Medicine)

NEW Postdoctoral Fellow – Molecular Cardiology (University of Illinois at Chicago)

Postdoctoral Researcher – Proliferative Responses in Cardiac Disease (University of Cambridge)

Senior Research Investigator – Multiple Sclerosis Research (Thomas Jefferson University)

Postdoctoral Positions – Signaling Mechanisms of Muscle Metabolism and Regeneration (McGovern Medical School at University of Texas Health Science Center)

Postdoctoral Scholar – Cardiovascular Genomics (Stanford Medicine)

Postdoctoral Research Associate – Cardiovascular Research (Old Dominion University)

Assistant Professor – Sarcoma or Skeletal Related Malignancies (University of California, Davis)

Assistant Specialist – Cardiovascular Research (University of California, Davis)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (University of California, Davis)

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