A5045940033- Kruppel-like factors research
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Cardiovascular Function and Risk Factors
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Sepsis Diagnosis and Treatment
- Genetic Syndromes and Imprinting
- Lipid metabolism and biosynthesis
- Nitric Oxide and Endothelin Effects
- Cardiac electrophysiology and arrhythmias
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Fibroblast Growth Factor Research
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Genomics, phytochemicals, and oxidative stress
- ATP Synthase and ATPases Research
- Cancer-related gene regulation
- Lipoproteins and Cardiovascular Health
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Cardiac Ischemia and Reperfusion
- Receptor Mechanisms and Signaling
- Vitamin C and Antioxidants Research
- Cardiac Valve Diseases and Treatments
University of Cincinnati Medical Center
2022-2025
University of Cincinnati
2022-2025
Center for Excellence in Education
2021-2023
Ohio University
2022-2023
Temple University
2014-2022
Temple College
2020
Stavros Niarchos Foundation
2015-2019
Columbia University
2008-2016
New York University
2014-2016
Friedrich Schiller University Jena
2016
Rationale: Efficient clearance of apoptotic cells (efferocytosis) is a prerequisite for inflammation resolution and tissue repair. After myocardial infarction, phagocytes are recruited to the heart promote dying cardiomyocytes. The molecular mechanisms efferocytosis cardiomyocytes in myocardium unknown. injured provides unique model examine relationships between subsequent resolution, remodeling, organ function. Objective: We set out identify cardiomyocyte engulfment by and, first time,...
We previously observed that treatment of mice with a dominant negative form cJun (dn-cJun) increased the expression genes involved in lipid metabolism and modulated nine microRNAs (miR). To investigate potential effect these miRs on metabolism, we performed studies cultured HepG2 cells. Transfection cells sense or antisense miR-370 miR-122 upregulated downregulated, respectively, transcription factor sterol-regulatory element binding protein 1c (SREBP-1c) enzymes diacylglycerol...
Background— Heart failure is associated with impaired myocardial metabolism a shift from fatty acids to glucose use for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart and mechanical unloading the failing myocardium corrects metabolism. Methods Results— analyzed serum 61 patients (body mass index, 26.5±5.1 kg/m 2 ; age, 51±12 years) obtained during left ventricular assist device implantation at explantation...
Movement of circulating fatty acids (FAs) to parenchymal cells requires their transfer across the endothelial cell (EC) barrier. The multiligand receptor cluster differentiation 36 (CD36) facilitates tissue FA uptake and is expressed in ECs such as myocytes adipocytes. Whether FAs dependent on EC or CD36, both, unknown. Using a cell-specific deletion approach, we show that EC, but not cell, CD36 increased fasting plasma postprandial triglycerides. EC-Cd36–KO mice had reduced radiolabeled...
Heart failure leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state cardiac remodeling. The deacetylase sirtuin 3 (SIRT3) plays a pivotal role in maintenance function through regulating acetylome. It is interesting note that unique systemic microRNAs have been shown play important remodeling by modulating key signaling elements myocardium.Cellular was analyzed human cardiomyocyte-like AC16 cells, acetylation levels...
Background— Cardiac dysfunction with sepsis is associated both inflammation and reduced fatty acid oxidation. We hypothesized that energy deprivation accounts for sepsis-related cardiac dysfunction. Methods Results— Escherichia coli lipopolysaccharide (LPS) administered to C57BL/6 mice (wild type) induced oxidation mRNA levels of peroxisome proliferator–activated receptor (PPAR)-α its downstream targets within 6–8 hours. Transgenic in which cardiomyocyte-specific expression PPARγ driven by...
Cardiomyopathy frequently complicates sepsis and is associated with increased mortality. Increased cardiac oxidative stress mitochondrial dysfunction have been observed during sepsis, but the mechanisms responsible for these abnormalities not determined. We hypothesized that NADPH oxidase 2 (NOX2) activation could be sepsis-induced cardiomyopathy. Treatment of isolated adult mouse cardiomyocytes low concentrations endotoxin lipopolysaccharide (LPS) total cellular reactive oxygen species...
Abnormal lipid metabolism may contribute to myocardial injury and remodeling. To determine whether accumulation of very long-chain ceramides occurs in human failing myocardium, we analyzed tissue serum from patients with severe heart failure (HF) undergoing placement left ventricular assist devices controls. Lipidomic analysis revealed increased total myocardium advanced HF. After unloading, these changes showed partial reversibility. Following infarction (MI), serine palmitoyl transferase...
Abnormal lipid metabolism may contribute to myocardial injury and remodeling. To determine whether accumulation of very long-chain ceramides occurs in human failing myocardium, we analyzed tissue serum from patients with severe heart failure (HF) undergoing placement left ventricular assist devices controls. Lipidomic analysis revealed increased total myocardium advanced HF. After unloading, these changes showed partial reversibility. Following infarction (MI), serine palmitoyl transferase...
Krüppel-like factors (KLFs) are deoxyribonucleic acid–binding transcriptional that regulate various pathways control metabolism and other cellular mechanisms. Various KLF isoforms have been associated with cellular, organ, or systemic metabolism. Altered expression activation of KLFs has linked to metabolic abnormalities, such as obesity diabetes, well heart failure. This review article summarizes the functions KLFs, networks different jointly in health disease.
Diabetic cardiomyopathy (DbCM) is a major complication in type-1 diabetes, accompanied by altered cardiac energetics, impaired mitochondrial function, and oxidative stress. Previous studies indicate that diabetes associated with increased expression of KLF5 (Krüppel-like factor-5) PPARα (peroxisome proliferator-activated receptor) regulate lipid metabolism.
Fatty acid oxidation is transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR)α and under normal conditions accounts for 70% of cardiac ATP content. Reduced Ppara expression during sepsis heart failure leads to reduced fatty myocardial energy deficiency. Many the transcriptional regulators are unknown.To determine role Krüppel-like factor 5 (KLF5) in regulation Ppara.We discovered that KLF5 activates gene via direct promoter binding. This blocked hearts septic mice...
ABSTRACT Both obesity and diabetes mellitus are associated with alterations in lipid metabolism as well a change bone homeostasis osteoclastogenesis. We hypothesized that increased fatty acid levels affect health by altering precursor cell differentiation osteoclast activation. Here we show palmitic (PA, 16:0) enhances receptor activator of NF-κB ligand (RANKL)-stimulated osteoclastogenesis is sufficient to induce even the absence RANKL. TNFα expression crucial for PA-induced...
Septic shock results from bacterial infection and is associated with multi-organ failure, high mortality, cardiac dysfunction. Sepsis causes both myocardial inflammation energy depletion. We hypothesized that reduced production a primary cause of ventricular dysfunction in sepsis. The JNK pathway activated sepsis has also been implicated impaired fatty acid oxidation several tissues. Therefore, we tested whether activation inhibits blocking would restore during LPS treatment. treatment...
Dual PPARα/γ agonists that were developed to target hyperlipidemia and hyperglycemia in patients with type 2 diabetes caused cardiac dysfunction or other adverse effects. We studied the mechanisms underlie cardiotoxic effects of a dual agonist, tesaglitazar, wild-type diabetic (leptin receptor–deficient, db/db) mice. Mice treated tesaglitazar-containing chow high-fat diet despite lower plasma triglycerides glucose levels. Expression PPARγ coactivator 1-α (PGC1α), which promotes mitochondrial...
Background Sepsis is the overwhelming host response to infection leading shock and multiple organ dysfunction. Cardiovascular complications greatly increase sepsis‐associated mortality. Although murine models are routinely used for preclinical studies, benefit of using genetically engineered mice in sepsis countered by discrepancies between human mouse pathophysiology. Therefore, recent guidelines have called standardization methods document We investigated course cardiac dysfunction...
Background: We previously showed that cardiomyocyte Krϋppel-like factor (KLF) 5 regulates cardiac fatty acid oxidation. As heart failure has been associated with altered oxidation, we investigated the role of KLF5 in lipid metabolism and pathophysiology ischemic failure. Methods: Using real-time polymerase chain reaction Western blot, expression changes a myocardial infarction (MI) mouse model tissue from patients 2D echocardiography, evaluated effect inhibition after MI using...
Progressive age-induced deterioration in the structure and function of cardiovascular system involves cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, endothelial dysfunction. These changes are driven by complex processes that interconnected, such as oxidative stress, mitochondrial autophagy, inflammation, telomere In recent years, advances research aging, including wide use animal models elucidated an abundance cell signaling pathways involved these...
Normal hearts have increased contractility in response to catecholamines. Because several lipids activate PKCs, we hypothesized that excess cellular would inhibit cardiomyocyte responsiveness adrenergic stimuli. Cardiomyocytes treated with saturated free fatty acids, ceramide, and diacylglycerol had reduced cAMP isoproterenol. This was associated PKC activation reduction of β-adrenergic receptor (β-AR) density. Pharmacological genetic inhibition prevented both palmitate-induced β-AR...