Science News from BCVS 2018

Cytosolic RBFox1 in Cardiac Pathological Remodeling
Chen Gao | UCLA-Los Angeles, Los Angeles, CA

• RESULTS: Cardiac expression of RBFox1c, an isoform of the nuclear RBFox1, results in suppression of proinflammatory genes and reduced cardiac fibrosis in response to myocardial infarct injury.
• Abstract for Gao (opens in new window)(link opens in new window)

Cytochrome b5 Reductase 3 Regulates Myoglobin Redox State and Controls Cardiac Function
Nolan Thorne Carew | University of Pittsburgh, Pittsburgh, PA

• RESULTS: For cardiomyocytes, Cyb5R3 expression may play a role as a heme-iron reductase, protecting against heme toxicity and damage within cells.
• Abstract for Carew (opens in new window)

Modeling of Diastolic Dysfunction in Induced Pluripotent Stem Cell-derived Cardiomyocytes From Hypertrophic Cardiomyopathy Patients
Haodi Wu | Stanford University, Stanford, CA

• RESULTS: Novel mechanisms for diastolic dysfunction, as well as possible treatment targets, were identified at the single-cell level using patient-specific induced pluripotent stem cell-derived cardiomyocytes from hypertrophic cardiomyopathy patients.
• Abstract for Wu (opens in new window)(link opens in new window)

MCL-1Matrix Promotes Mitochondrial Fusion and Protects Against TAC Induced Hypertrophy
Leonardo J Leon |University of California San Diego, San Diego, CA

• RESULTS: Overexpression of the cardiac MCL-1Matrix protein promotes mitochondrial enlargement in heart muscle cells, reducing stress during cardiac pressure overload.
• Abstract for Leon (opens in new window)(link opens in new window)

Mechanistic Insights into Duchenne Muscular Dystrophy-Associated Cardiomyopathy
Tara Tassin | UT Southwestern Medical Center, Dallas, TX

• RESULTS: Mechanisms for Duchenne Muscular Dystrophy-associated cardiomyopathy identify dysregulation of cardiac signaling pathways.
• Abstract for Tassin (opens in new window)(link opens in new window)

AAV-Exosomes: A Novel Platform for Myocardial Gene Delivery for Cardioprotection
Marta Adamiak | Icahn School of Medicine at Mount Sinai, New York, NY

• RESULTS: Carrier exosomes show promise as a delivery option for adeno-associated virus (AAVs-based gene therapy delivery; avoid natural immunity.
• Abstract for Adamiak (opens in new window)(link opens in new window)
• AHA News article: Scientists may have cleared gene therapy hurdle (opens in new window)(link opens in new window)

Effective Three-element Windkessel Model based on Doppler Ultrasound Images for Noninvasive Quantification of Trans-stenotic Pressure Gradient in Aortorenal System
Monsurul Khan | Indiana University-Purdue University Indianapolis, Indianapolis, IN

• RESULTS: Image-based computational hemodynamics (ICH) tool may aid stenting decision-making by non-invasively measuring aortorenal pressure gradients in renal artery stenosis (RAS).
• Abstract for Khan (opens in new window)(link opens in new window)

Effects of Microgravity on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function
Alexa Wnorowski | Stanford University, Stanford, CA

• RESULTS: Microgravity experienced on the International Space Station impacts heart function at a cellular level, and includes changes in gene expression, structure and function.
• Abstract for Wnorowski (opens in new window)(link opens in new window)

Exclusion of Major Cell Types in the Murine Heart Enriches for Cardiac Pericytes
Shuin Park | University of California, Los Angeles, Los Angeles, CA

• RESULTS: Exclusion of other cell-types and RNA-sequencing has identified subpopulations of cardiac pericytes; further study needed to determine their different functions.
• Abstract for Park (opens in new window)(link opens in new window)

Perm1 is a Novel Regulator of Mitochondrial Energetics in Cardiomyocytes
Junco S Warren | University of Utah, Salt Lake Cty, UT

• RESULTS: PERM 1 has a novel role in mitochondrial energetics regulation. Downregulation of PERM 1 in cardiomyocytes may reduce mitochondrial function during heart failure.
• Abstract for Warren (opens in new window)(link opens in new window)

Alpha-Ketoglutarate Dehydrogenase Inhibition by the Oncometabolite D2-HG Causes Proteome and Metabolome Remodeling in Myocytes
Anja Karlstaedt | McGovern Medical School at UTHealth, Houston, TX

• RESULTS: The oncometabolite D-2-hydroxyglutarate (D2-HG) inhibits alpha-ketoglutarate dehydrogenase inhibition in myocytes, resulting in an increase in proteomic remodeling and metabolomic changes.
• Abstract for Karlstaedt (opens in new window)(link opens in new window)

Regulation of Cardiac Mitochondrial Function by Chaperone Mediated Autophagy
Yun Chen | Albert Einstein College of Medicine, Bronx, NY

• RESULTS: Activation of chaperone mediated autophagy by cardiac overload stresses may result in heart failure.
• Abstract for Chen (opens in new window)(link opens in new window)

Mybphl is a Novel Myofilament Component Implicated in Arrhythmia and Dilated Cardiomyopathy
David Y Barefield | Northwestern University, Chicago, IL

• RESULTS: Loss of the novel myofilament component, MyBP-HL, impaired the ventricular conduction system and was associated with ventricular arrhythmia and dilated cardiomyopathy.
• Abstract for Barefield (opens in new window)(link opens in new window)

Cardiomyocyte Braf Promotes Hypertrophy and is Required for Hypertrophic Adaptation to Hypertension in Mice In Vivo, but Raf Inhibitors Have Differential Effects
Daniel N Meijles | St George's University of London, London, United Kingdom

• RESULTS: Raf inhibitors (Rafi), used to inhibit Braf mutations in cancer, demonstrated differing effects on the heart compared to the protective effects of non-mutated Braf.
• Abstract for Meijles (opens in new window)(link opens in new window)

The Ufm1 Specific Ligase 1 Regulates Endoplasmic Reticulum Homeostasis and Protects Against Heart Failure
Huabo Su | Augusta University, Augusta, GA

• RESULTS: The Ufm1 system may be key to cardiac homeostasis by regulation of endoplasmic reticulum function; Ufl1 may have a role in heart failure protection.
• Abstract for Su (opens in new window)(link opens in new window)

WINNER
Chromatin Microenvironments With Distinct Functionality During Cardiac Stress
Manuel Rosa-Garrido | UCLA, Los Angeles, CA

• RESULTS: Epigenetic features contributed to chromatin microenvironments with distinct functions that are involved in heart failure.
• Abstract for Rosa-Garrido (opens in new window)(link opens in new window)
• See Rosa-Garrido's interview with BCVS volunteer Ronglih Liao, PhD (opens in new window) (link opens in new window)

Steering Fibroblast Phenotype to Promote Left Ventricular Scar Maturation and Function Post-MI
Lisandra E de Castro Brás | East Carolina University, Greenville, NC

• RESULTS: Following a heart attack, p1158/59 from the extracellular matrix may regulate, in part, the maturation and stabilization of scar formation and tissue remodeling.
• Abstract for de Castro Brás (opens in new window)(link opens in new window)

A Role for Brain-derived Neurotrophic Factor in Duchenne Cardiomyopathy
Cristi L Galindo | Vanderbilt University Medical Center, Nashville, TN

• RESULTS: Brain-derived neurotrophic factor (BDNF) may be protective for cardiomyopathy and could offer therapy development options for Duchenne cardiomyopathy.
• Abstract for Galindo (opens in new window)(link opens in new window)