A5051877816- Cardiac Fibrosis and Remodeling
- Cardiovascular Function and Risk Factors
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Connexins and lens biology
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Cardiomyopathy and Myosin Studies
- Nitric Oxide and Endothelin Effects
- Cardiac Ischemia and Reperfusion
- Cancer, Hypoxia, and Metabolism
- Molecular Biology Techniques and Applications
- Sirtuins and Resveratrol in Medicine
- Electrostatic Discharge in Electronics
- Mitochondrial Function and Pathology
- Sexual function and dysfunction studies
- Sexuality, Behavior, and Technology
- Pulmonary Hypertension Research and Treatments
- Maternal and fetal healthcare
- Plant and animal studies
- Blood Coagulation and Thrombosis Mechanisms
- Animal Behavior and Reproduction
- Extracellular vesicles in disease
- Redox biology and oxidative stress
- Electrochemical sensors and biosensors
Cedars-Sinai Smidt Heart Institute
2018-2024
Cedars-Sinai Medical Center
2017-2024
Justus-Liebig-Universität Gießen
2011-2015
National Heart Lung and Blood Institute
2014
National Institutes of Health
2014
Macquarie University
2010
Connexin 43 (Cx43) is present at the sarcolemma and inner membrane of cardiomyocyte subsarcolemmal mitochondria (SSM). Lack or inhibition mitochondrial Cx43 associated with reduced potassium influx, which might affect respiration. Therefore, we analysed importance for oxygen consumption. Acute in rat left ventricular (LV) SSM by 18α glycyrrhetinic acid (GA) mimetic peptides (Cx43-MP) ADP-stimulated complex I respiration ATP generation. Chronic reduction conditional knockout mice...
S-nitrosation (SNO) of connexin 43 (Cx43)-formed channels modifies dye uptake in astrocytes and gap junctional communication endothelial cells. Apart from forming at the plasma membrane several cell types, Cx43 is also located inner myocardial subsarcolemmal mitochondria (SSM), but not interfibrillar (IFM). The absence or pharmacological blockade mitochondrial (mtCx43) reduces potassium uptake. Lack mtCx43 associated with loss endogenous cardioprotection by ischemic preconditioning (IPC),...
Abstract Aims Cardiomyopathy patients are prone to ventricular arrhythmias (VA) and sudden cardiac death. Current therapies prevent VA include radiofrequency ablation destroy slowly conducting pathways of viable myocardium which support re-entry. Here, we tested the reverse concept, namely that boosting local tissue viability in zones slow conduction might eliminate suppress ischaemic cardiomyopathy. Methods results Exosomes extracellular vesicles laden with bioactive cargo. secreted by...
ABSTRACT Newts can regenerate amputated limbs and cardiac tissue, unlike mammals which lack broad regenerative capacity. Several signaling pathways involved in cell proliferation, differentiation survival during newt tissue regeneration have been elucidated, however the factors that coordinate between cells, as well conservation of these other animals, are not defined. Here we report media conditioned by limb explant cells (A1 cells) protect mammalian cardiomyocytes from oxidative...
Rationale: Phosphorylation of sarcomeric proteins has been implicated in heart failure with preserved ejection fraction (HFpEF); such changes may contribute to diastolic dysfunction by altering contractility, cardiac stiffness, Ca 2+ -sensitivity, and mechanosensing. Treatment cardiosphere-derived cells (CDCs) restores normal function, attenuates fibrosis inflammation, improves survival a rat HFpEF model. Objective: that underlie those reversed CDC therapy, focus on the subproteome were...
Abstract Connexin 43 (Cx43), which is highly expressed in the heart and especially cardiomyocytes, interferes with expression of nitric oxide synthase ( NOS ) isoforms. Conversely, Cx43 gene down‐regulated by derived from inducible . Thus, a complex interplay between appears to exist. As cardiac mitochondria are supposed contain , we now investigated isoforms production rate isolated wild‐type Cx43‐deficient (Cx43 Cre‐ER(T)/fl mice hearts. Mitochondria were hearts using differential...
Abstract Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery a novel micropeptide, dubbed slitharin (Slt), conditioned media from Cardiosphere‐derived cells (CDCs), therapeutic cardiac stromal type. Experimental design: We performed mass spectrometry peptide‐enriched fractions CDCs and therapeutically inert type (human dermal fibrobasts). then evaluated capacity candidate peptide using vitro model cardiomyocyte...
Abstract Astrocytes protect neurons during cerebral injury through several postulated mechanisms. Recent therapeutic attention has focused on enhancing or augmenting the neuroprotective actions of astrocytes but in some instances can assume a neurotoxic phenotype. The signaling mechanisms that drive toward protective versus toxic phenotype are not fully known cell–cell via proteases acting cell‐specific receptors underlies critical mechanistic steps neurodevelopment and disease. protease...
Background Preeclampsia, a leading cause of maternal and fetal mortality morbidity, is characterized by an increase in S-nitrosylated proteins reactive oxygen species, suggesting pathophysiologic role for dysregulation nitrosylation nitrosative stress. Methods Results Here, we show that mice lacking S-nitrosoglutathione reductase (
Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, pulmonary congestion and exercise intolerance. Previous preclinical studies show that treatment cardiosphere-derived cells (CDCs) improves function, attenuates arrhythmias prolongs survival in a rat HFpEF model. Here we characterize the myocardial proteome function HFpEF, without CDC therapy. As an initial strategy for identifying pathways worthy of further mechanistic...
Objectives Binding of nitric oxide (NO) to a cysteine thiol is termed S‐nitrosylation, which emerging as an important means NO‐mediated signal transduction independent stimulation soluble guanylate cyclase. However, the impact S‐nitrosylation on erectile function remains unclear. redox sensitive post‐translational modification, thought be promoted by reactive oxygen species (ROS). Protein levels are regulated in part S‐nitrosoglutatione reductase (GSNOR), acts de‐nitrosylate protein thiols....
Metabolic rewiring is a hallmark of cancer and muscle cells. In isocitrate dehydrogenase 1 2 mutant tumors, increased plasma levels the oncometabolite D-2-hydroxyglutarate (D2-HG) are associated with systemic effects, including myopathy. Our recent in vivo work showed that D2-HG supply by IDH-mutant cells causes heart skeletal atrophy, decreases cellular ATP NADH. Although failure cachexia commonly chemotherapy, survivors have 5-fold risk independent any cytostatic treatment. The connection...
ABSTRACT Preeclampsia (PE), a leading cause of maternal and fetal mortality morbidity, is characterized by an increase in S-nitrosylated (SNO) proteins reactive oxygen species (ROS), suggesting pathophysiologic role for dysregulation nitrosylation nitrosative stress. Here we show that mice lacking S-nitrosoglutathione reductase ( GSNOR −/− ), denitrosylase regulating protein S-nitrosylation, exhibit PE phenotype, including hypertension, proteinuria, renal pathology, cardiac concentric...
With PAH, the fate of RV is a major determinant survival.The initially responds by adaptive and physiologic hypertrophy to maintain cardiac output.However, over time maladaptive changes ensue in muscle, impair both diastolic systolic function, with eventual development overt right heart failure.Pathobiologic abnormalities maladapted muscle include: decreased vascular capillarity, increased fibrosis, inflammation oxidative stress, altered metabolism cardiomyocyte death.There are currently no...