Dennis M Abraham

Journal Article Am J Physiol Heart Circ Physiol · November 1, 2024 Left ventricular hypertrophy (LVH) caused by chronic pressure overload with subsequent pathological remodeling is a major cardiovascular risk factor for heart failure and mortality. The role of deubiquitinases in LVH has not been well characterized. To def ... Full text Link to item Cite

Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure.

Journal Article iScience · April 15, 2022 The complex and inaccessible space radiation environment poses an unresolved risk to astronaut cardiovascular health during long-term space exploration missions. To model this risk, healthy male c57BL/6 mice aged six months (corresponding to an astronaut o ... Full text Link to item Cite

Early Identification of Patients at Risk for Incident Heart Failure With Preserved Ejection Fraction: Novel Approach to Echocardiographic Trends.

Journal Article J Card Fail · September 2021 BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) continues to increase in prevalence with a 50% mortality rate within 3 years of diagnosis, but lacking effective evidence-based therapies. Specific echocardiographic markers are not typical ... Full text Link to item Cite

Characterization of cardiovascular injury in mice following partial-heart irradiation with clinically relevant dose and fractionation.

Journal Article Radiother Oncol · April 2021 BACKGROUND AND PURPOSE: Late cardiac toxicity is a major side effect of radiation therapy (RT) for breast cancer. We developed and characterized a mouse model of radiation-induced heart disease that mimics the dose, fractionation, and beam arrangement of l ... Full text Link to item Cite

Exercise protects against cardiac and skeletal muscle dysfunction in a mouse model of inflammatory arthritis.

Journal Article J Appl Physiol (1985) · March 1, 2021 Rheumatoid arthritis (RA) is a systemic inflammatory arthritis impacting primarily joints and cardiac and skeletal muscle. RA's distinct impact on cardiac and skeletal muscle tissue is suggested by studies showing that new RA pharmacologic agents strongly ... Full text Link to item Cite

Direct Actions of AT1 (Type 1 Angiotensin) Receptors in Cardiomyocytes Do Not Contribute to Cardiac Hypertrophy.

Journal Article Hypertension · February 2021 Activation of AT1 (type 1 Ang) receptors stimulates cardiomyocyte hypertrophy in vitro. Accordingly, it has been suggested that regression of cardiac hypertrophy associated with renin-Ang system blockade is due to inhibition of cellular actions of Ang II i ... Full text Link to item Cite

Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure.

Journal Article Circ Res · September 25, 2020 RATIONALE: Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains ... Full text Link to item Cite

β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.

Journal Article Cell · June 11, 2020 Small molecule neurotensin receptor 1 (NTSR1) agonists have been pursued for more than 40 years as potential therapeutics for psychiatric disorders, including drug addiction. Clinical development of NTSR1 agonists has, however, been precluded by their seve ... Full text Link to item Cite

Pulmonary Hypertension Subtypes and Mortality in CKD.

Journal Article Am J Kidney Dis · May 2020 RATIONALE & OBJECTIVE: Pulmonary hypertension (PH) contributes to cardiovascular disease and mortality in patients with chronic kidney disease (CKD), but the pathophysiology is mostly unknown. This study sought to estimate the prevalence and consequences o ... Full text Open Access Link to item Cite

Lack of Thy1 defines a pathogenic fraction of cardiac fibroblasts in heart failure.

Journal Article Biomaterials · April 2020 In response to heart injury, inflammation, or mechanical overload, quiescent cardiac fibroblasts (CFs) can become activated myofibroblasts leading to pathological matrix remodeling and decline in cardiac function. Specific targeting of fibroblasts may thus ... Full text Link to item Cite

TASK-1 and TASK-3 channels modulate pressure overload-induced cardiac remodeling and dysfunction.

Journal Article Am J Physiol Heart Circ Physiol · March 1, 2020 Tandem pore domain acid-sensitive K+ (TASK) channels are present in cardiac tissue; however, their contribution to cardiac pathophysiology is not well understood. Here, we investigate the role of TASK-1 and TASK-3 in the pathogenesis of cardiac dysfunction ... Full text Link to item Cite

Evaluation of antihypertensive drugs in combination with enzyme replacement therapy in mice with Pompe disease.

Journal Article Mol Genet Metab · February 2020 UNLABELLED: Pompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA) leading to progressive myopathy. Enzyme replacement therapy (ERT) with recombinant human (rh) GAA has limitations, including inefficient uptake of rhGAA in skeletal ... Full text Open Access Link to item Cite

The deubiquitinase ubiquitin-specific protease 20 is a positive modulator of myocardial β1-adrenergic receptor expression and signaling.

Journal Article J Biol Chem · February 15, 2019 Reversible ubiquitination of G protein-coupled receptors regulates their trafficking and signaling; whether deubiquitinases regulate myocardial β1-adrenergic receptors (β1ARs) is unknown. We report that ubiquitin-specific protease 20 (USP20) deubiquitinate ... Full text Link to item Cite

The two-pore domain potassium channel TREK-1 mediates cardiac fibrosis and diastolic dysfunction.

Journal Article J Clin Invest · November 1, 2018 Cardiac two-pore domain potassium channels (K2P) exist in organisms from Drosophila to humans; however, their role in cardiac function is not known. We identified a K2P gene, CG8713 (sandman), in a Drosophila genetic screen and show that sandman is critica ... Full text Link to item Cite

Ablation of Sirtuin5 in the postnatal mouse heart results in protein succinylation and normal survival in response to chronic pressure overload.

Journal Article J Biol Chem · July 6, 2018 Mitochondrial Sirtuin 5 (SIRT5) is an NAD+-dependent demalonylase, desuccinylase, and deglutarylase that controls several metabolic pathways. A number of recent studies point to SIRT5 desuccinylase activity being important in maintaining cardiac function a ... Full text Link to item Cite

Ghrelin receptor antagonism of hyperlocomotion in cocaine-sensitized mice requires βarrestin-2.

Journal Article Synapse · January 2018 The "brain-gut" peptide ghrelin, which mediates food-seeking behaviors, is recognized as a very strong endogenous modulator of dopamine (DA) signaling. Ghrelin binds the G protein-coupled receptor GHSR1a, and administration of ghrelin increases the rewardi ... Full text Link to item Cite

Sirtuin 5 is required for mouse survival in response to cardiac pressure overload.

Journal Article J Biol Chem · December 1, 2017 In mitochondria, the sirtuin SIRT5 is an NAD+-dependent protein deacylase that controls several metabolic pathways. Although a wide range of SIRT5 targets have been identified, the overall function of SIRT5 in organismal metabolic homeostasis remains uncle ... Full text Link to item Cite

Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of β-adrenergic receptor signaling.

Journal Article JCI Insight · September 7, 2017 The oncoprotein Mdm2 is a RING domain-containing E3 ubiquitin ligase that ubiquitinates G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, thereby regulating β-adrenergic receptor (βAR) signaling and endocytosis. Previous studies showed that cardi ... Full text Open Access Link to item Cite

Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich's ataxia cardiomyopathy model.

Journal Article JCI Insight · July 20, 2017 Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which ... Full text Link to item Cite

β-Arrestin mediates the Frank-Starling mechanism of cardiac contractility.

Journal Article Proc Natl Acad Sci U S A · December 13, 2016 The Frank-Starling law of the heart is a physiological phenomenon that describes an intrinsic property of heart muscle in which increased cardiac filling leads to enhanced cardiac contractility. Identified more than a century ago, the Frank-Starling relati ... Full text Link to item Cite

TWIK-Related Acid-Sensitive K+ Channels Affect the Development of Aortic Root Aneurysms in Mice

Conference CIRCULATION · November 11, 2016 Link to item Cite

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice.

Journal Article J Vis Exp · September 17, 2015 Cardiac pressure-volume loop analysis is the "gold-standard" in the assessment of load-dependent and load-independent measures of ventricular systolic and diastolic function. Measures of ventricular contractility and compliance are obtained through examina ... Full text Link to item Cite

Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1 Receptors.

Journal Article Circulation · June 16, 2015 BACKGROUND: Whether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the angiotensin ... Full text Link to item Cite

TREK-1 Modulates Fibrosis & Diastolic Dysfunction Through Activation of Stress-Activated Kinases

Conference CIRCULATION · November 25, 2014 Link to item Cite

Inhibition of the cardiomyocyte-specific troponin I-interacting kinase limits oxidative stress, injury, and adverse remodeling due to ischemic heart disease.

Journal Article Circ Res · March 14, 2014 Ischemia–reperfusion injury is strongly associated with increased oxidative stress, mitochondrial dysfunction, and cell death. These processes are diminished in an animal model of ischemia–reperfusion by the genetic loss or pharmacological inhibition of tr ... Full text Link to item Cite

Disruption of sarcoendoplasmic reticulum calcium ATPase function in Drosophila leads to cardiac dysfunction.

Journal Article PLoS One · 2013 Abnormal sarcoendoplasmic reticulum Calcium ATPase (SERCA) function has been associated with poor cardiac function in humans. While modifiers of SERCA function have been identified and studied using animal models, further investigation has been limited by ... Full text Link to item Cite

β-Arrestin-biased AT1R stimulation promotes cell survival during acute cardiac injury.

Journal Article Am J Physiol Heart Circ Physiol · October 15, 2012 Pharmacological blockade of the ANG II type 1 receptor (AT1R) is a common therapy for treatment of congestive heart failure and hypertension. Increasing evidence suggests that selective engagement of β-arrestin-mediated AT1R signaling, referred to as biase ... Full text Link to item Cite

Cardiomyopathy is associated with ribosomal protein gene haplo-insufficiency in Drosophila melanogaster.

Journal Article Genetics · November 2011 The Minute syndrome in Drosophila melanogaster is characterized by delayed development, poor fertility, and short slender bristles. Many Minute loci correspond to disruptions of genes for cytoplasmic ribosomal proteins, and therefore the phenotype has been ... Full text Link to item Cite

A method to measure myocardial calcium handling in adult Drosophila.

Journal Article Circ Res · May 27, 2011 RATIONALE: Normal cardiac physiology requires highly regulated cytosolic Ca(2+) concentrations and abnormalities in Ca(2+) handling are associated with heart failure. The majority of approaches to identifying the components that regulate intracellular Ca(2 ... Full text Link to item Cite

Hostility and platelet reactivity in individuals without a history of cardiovascular disease events.

Journal Article Psychosom Med · September 2009 OBJECTIVE: To examine the association between hostility and platelet reactivity in individuals without a prior history of cardiovascular disease (CVD) events. Hostility is associated with incident CVD events, independent of traditional risk factors. Increa ... Full text Link to item Cite

Relative utility of home, ambulatory, and office blood pressures in the prediction of end-organ damage.

Journal Article Am J Hypertens · May 2007 BACKGROUND: Home blood pressure (HBP) monitoring plays an increasingly important role in the diagnosis and treatment of hypertension. We evaluated the independent value of HBP compared with ambulatory blood pressure (ABP) and office blood pressure (OBP) in ... Full text Link to item Cite

Effect of anger provocation on endothelium-dependent and -independent vasodilation.

Journal Article Am J Cardiol · March 15, 2007 Anger is an independent predictor of coronary heart disease events, although the mechanisms for this relation are unclear. The effects of an anger-provoking interview compared with a neutral interview on endothelium-dependent and -independent vasodilation ... Full text Link to item Cite

Superiority of ambulatory to physician blood pressure is not an artifact of differential measurement reliability.

Journal Article Blood Press Monit · December 2006 BACKGROUND: Ambulatory blood pressure is a better predictor of target organ damage and the risk of adverse cardiovascular events than office measurements. Whether this is due to the greater reliability owing to the larger number of measurements that are us ... Full text Link to item Cite