Muscle Cell News Volume 4.25 | Jul 22 2019

TOP STORY

Activation of PDGF Pathway Links LMNA Mutation to Dilated Cardiomyopathy

Researchers modeled Lamin A/C (LMNA)-related dilated cardiomyopathy in vitro using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Electrophysiological studies showed that the mutant iPSC-CMs displayed aberrant calcium homeostasis that led to arrhythmias at the single-cell level. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

CARDIAC MUSCLE CELLS

Dual Stem Cell Therapy Synergistically Improves Cardiac Function and Vascular Regeneration Following Myocardial Infarction

Epicardially implanted human mesenchymal stem cell-loaded patches provided a complimentary microenvironment which enhanced vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improved the retention and engraftment of intramyocardially injected cardiomyocytes derived from human induced pluripotent stem cells which ultimately restored the cardiac function. [Nat Commun] Full Article

Different Antioxidant Efficacy of Two Mn^II-Containing Superoxide Anion Scavengers on Hypoxia/Reoxygenation-Exposed Cardiac Muscle Cells

A new oxidative stress due to excess superoxide anion-scavenging Mn^II complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing two quinoline units, designed to improve complex stability and cell permeability, was compared to parental Mn^II complex with methyls replacing quinolines. [Sci Rep] Full Article

2-Cl-C.OXT-A Stimulates Contraction through the Suppression of Phosphodiesterase Activity in Human Induced Pluripotent Stem Cell-Derived Cardiac Organoids

Cardiac organoids with fibroblasts, human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs), and hiPSC-derived endothelial cells were cultured until they started beating. The beating and contraction of organoids were observed before and after the application of 2-Cl-C.OXT-A. [PLoS One] Full Article

SKELETAL MUSCLE CELLS

Fate Decision of Satellite Cell Differentiation and Self-Renewal by miR-31-IL34 Axis

MiR-31 was pivotal for satellite cell proliferation, and its deletion promoted asymmetric cell fate segregation of proliferating cells, resulting in enhanced myogenic commitment and re-entry into quiescence. Further analysis revealed that miR-31 post-transcriptionally suppressed interleukin 34 (IL34) mRNA, the protein product of which activated JAK-STAT3 signaling required for myogenic progression. [Cell Death Differ] Abstract

Elevated H3K27ac in Aged Skeletal Muscle Leads to Increase in Extracellular Matrix and Fibrogenic Conversion of Muscle Satellite Cells

Researchers examined the changes of a panel of histone modifications and found H3K27ac was markedly increased in aged human skeletal muscle tissues. Further analyses uncovered that the H3K27ac increase and enhancer activation were associated with the up-regulation of extracellular matrix genes; this may have resulted in alteration of the niche environment for skeletal muscle stem cells which caused decreased myogenic potential and fibrogenic conversion of satellite cells. [Aging Cell] Full Article

A Mitochondrial Delivery System Using Liposome-Based Nanocarriers That Target Myoblast Cells

The authors report on attempts to develop liposome-based carriers for mitochondrial delivery using mouse myoblasts by varying the lipid composition of the carriers. They found that a liposome that contained an optimal lipid modified with the KALA peptide was the most effective nanocarrier for achieving mitochondrial delivery in C2C12 cells. [Mitochondrion] Abstract

Maduramicin Inactivation of Akt Impairs Autophagic Flux Leading to Accumulated Autophagosomes-Dependent Apoptosis in Skeletal Myoblast Cells

Investigators showed that maduramicin (Mad) induced apoptosis dose-dependently, which was associated with impaired autophagic flux in skeletal myoblast cells. This was supported by the findings that Mad treatment resulted in the increase of autophagosomes with a concomitant elevation of LC3-II and p62 in the cells. [Int J Biochem Cell Biol] Abstract

SMOOTH MUSCLE CELLS

Hypoxia Inducible Factor 1α in Vascular Smooth Muscle Cells Promotes Angiotensin II-Induced Vascular Remodeling via Activation of CCL7-Mediated Macrophage Recruitment

In the angiotensin II (Ang II)-induced vascular remodeling model, hypoxia-inducible factor 1α (HIF1α) was increased and activated in vascular smooth muscle cells (VSMCs). Selective genetic disruption of Hif1a in VSMCs markedly ameliorated Ang II-induced vascular remodeling, as revealed by decreased blood pressure, aortic thickness, collagen deposition, inflammation, and aortic stiffness. [Cell Death Dis] Full Article

The Flagellin-TLR5-Nox4 Axis Promotes the Migration of Smooth Muscle Cells in Atherosclerosis

To investigate the molecular mechanism by which the TLR5-NADPH oxidase 4 (Nox4) cascade mediates smooth muscle cell (SMC) migration, scientists analyzed the signaling cascade in primary vascular (V) SMCs from wild-type (WT) or Nox4 KO mice. Stimulation of VSMCs from Nox4 KO mice with flagellin failed to induce H₂O₂ production and Rac activation compared with stimulation of VSMCs from WT mice. [Exp Mol Med] Full Article

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CRISPR Craze to Transform Cardiac Biology

CRISPR-based strategies that act independent of the homology-directed repair pathway could help circumvent issues of modifying the genome of postmitotic cardiomyocytes, which is currently limiting its utility in the heart. The authors review current applications and future potential for the use of CRISPR to study cardiac biology and disease. [Trends Mol Med] Full Article

Modeling Hypertrophic Cardiomyopathy: Mechanistic Insights and Pharmacological Intervention

Investigators compare recent progress in unveiling multiple hypertrophic cardiomyopathy (HCM) mechanisms in different models, highlighting similarities and discrepancies. They explore how insight is facilitating the design of new HCM therapeutics, including those that regulate metabolism, contraction and heart rhythm, providing a future perspective for treatment of HCM. [Trends Mol Med] Full Article

Mechanosensitive Pathways Controlling Translation Regulatory Processes in Skeletal Muscle and Implications for Adaptation

The ability for myofibers to sense and respond appropriately to mechanical signals is one of the primary determinants of the skeletal muscle phenotype. In response to a change in mechanical load, muscle cells alter their protein metabolism, primarily through the regulation of protein synthesis rate. [J Appl Physiol] Abstract

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MyoKardia Announces HCM Program Updates: Accelerates Timing for Mavacamten Topline Phase III Data; Re-Acquires US Royalty Rights to HCM Programs from Sanofi

MyoKardia, Inc.announced updates related to its hypertrophic cardiomyopathy treatment portfolio, including lead therapeutic candidate, mavacamten. Patient screening has closed for the Phase III EXPLORER-HCM registrational clinical study to assess the effect of mavacamten in treating patients with obstructive hypertrophic cardiomyopathy. [MyoKardia] Press Release

MDA Awards Venture Philanthropy Funding to Dr. Rachelle Crosbie to Develop a Novel Membrane-Stabilizing Drug for Duchenne Muscular Dystrophy

The Muscular Dystrophy Association (MDA) has awarded MDA Venture Philanthropy funding totaling $389,000 over two years to Rachelle H. Crosbie, PhD, professor and chair of Integrative Biology and Physiology at the University of California, Los Angeles. The award will support the development of a small molecule drug that increases expression of sarcospan, a protein that may help to prevent the muscle damage that occurs in Duchenne muscular dystrophy. [Muscular Dystrophy Association] Press Release

Mystery Surrounds Ouster of Chinese Researchers from Canadian Laboratory

Canadian researchers are reacting with puzzlement to the news that a “policy breach” has caused the nation’s only high-containment disease laboratory to bar a prominent Chinese Canadian virologist, her biologist husband, and a number of students from the facility. [ScienceMagazine] Editorial

The Plan to Mine the World’s Research Papers

Carl Malamud is on a crusade to liberate information locked up behind paywalls — and his campaigns have scored many victories. Now, the 60-year-old American technologist is turning his sights on a new objective: freeing paywalled scientific literature. And he thinks he has a legal way to do it. [Nature News] Editorial

NEW Wnt Signaling Networks in Development, Disease and Regeneration
August 11-16, 2019
West Dover, Vermont, United States

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NEW Tenure-Track Faculty Position – Integrative Biology and Physiology (University of California)

NEW Postdoctoral Fellow – Cardiovascular Biology (Oklahoma Medical Research Foundation)

NEW Senior Scientist – Gene Therapy in Muscle Cells (Shape Therapeutics)

NEW Associate Scientist – Drug Discovery Program (Casma Therapeutics)

Postdoctoral Fellowship – Molecular Mechanisms of Atrial Fibrillation (Electrophysiology and Heart Modeling Institute)

Postdoctoral Fellow – Cardiovascular Biology (Oklahoma Medical Research Foundation)

Research Scientist – Cellular Electrophysiology (Duke University)

Postdoctoral Researcher – Muscle Atrophy and Metabolism (McGill University)

Postdoctoral Researchers – Cardiovascular Studies (Virginia Tech)

Postdoctoral Fellow – Facioscapulohumeral Muscular Dystrophy Research (Pfizer)

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