A5101870315- Lipid metabolism and disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cancer, Lipids, and Metabolism
- Cholesterol and Lipid Metabolism
- Lipoproteins and Cardiovascular Health
- Fatty Acid Research and Health
- Atherosclerosis and Cardiovascular Diseases
- Diabetes and associated disorders
- Eicosanoids and Hypertension Pharmacology
- Pancreatic function and diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Clinical Laboratory Practices and Quality Control
- Cardiovascular Health and Risk Factors
- Metabolism, Diabetes, and Cancer
- Hemoglobinopathies and Related Disorders
- Systemic Lupus Erythematosus Research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- COVID-19 Clinical Research Studies
- Caveolin-1 and cellular processes
- Psoriasis: Treatment and Pathogenesis
- SARS-CoV-2 and COVID-19 Research
- Cardiovascular Disease and Adiposity
- Lipid metabolism and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Antioxidant Activity and Oxidative Stress
National Heart Lung and Blood Institute
2016-2025
National Institutes of Health
2016-2025
Mayo Clinic
2023
Wake Forest University
2023
University of Minnesota Rochester
2023
Mayo Clinic in Arizona
2023
Philadelphia University
2019
National Institutes of Health Clinical Center
2004-2017
Institut des Maladies Métaboliques et Cardiovasculaires
2017
Centre National de la Recherche Scientifique
2017
Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for causal association between triglycerides (TG), TG-rich lipoproteins (TRL), TRL remnants, increased risk myocardial infarction, ischaemic stroke, aortic valve stenosis. These data also indicate that their remnants may contribute significantly to residual cardiovascular patients on optimized low-density lipoprotein (LDL)-lowering therapy. This...
Cellular and plasma lipid levels are tightly controlled by complex gene regulatory mechanisms. Elevated content, or hyperlipidemia, is a significant risk factor for cardiovascular morbidity mortality. MicroRNAs (miRNAs) posttranscriptional regulators of expression have emerged as important modulators homeostasis, but the extent their role has not been systematically investigated. In this study we performed high-throughput small RNA sequencing detected ≈ 150 miRNAs in mouse liver. We then...
GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, disease associated with increased risk, provides a model to study biomarkers (CVD). Whether GlycA associates psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein is unknown.To investigate the relationships between CVD.Patients controls (n=412) participated 2-stage study. We measured by nuclear magnetic resonance spectroscopy. National...
A number of studies have shown that autologous and allogeneic hematopoietic cell transplantation (HCT) contribute to an increased incidence cardiovascular disease (CVD) worsening risk factors could further CVD over time. These observations, combined with a notable increase in the survivors after HCT recent years, highlight need for aimed at modifying or preventing these outcomes by changing specific approaches and/or post-HCT interventions. To address issues, National Heart, Lung Blood...
While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the “complosome,” functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular is also nonredundant for activity myeloid immune cells currently unknown. Here, we show that monocytes and macrophages constitutively express component (C) 5 generate autocrine C5a via formation an C5 convertase. Cholesterol crystal sensing by induced...
Abstract Several variants of SARS-CoV-2 have emerged. Those with mutations in the angiotensin-converting enzyme (ACE2) receptor binding domain (RBD) are associated increased transmission and severity. In this study, we developed both antibody quantification functional neutralization assays. Analyses COVID-19 convalescent diagnostic cohorts strongly support use RBD levels as an excellent surrogate to biochemical activities. Data further revealed that samples from mRNA vaccinated individuals...
Receptors that endocytose high-density lipoproteins (HDL) have been elusive. Here yolk-sac endoderm-like cells were used to identify an endocytic receptor for HDL. The was isolated by HDL affinity chromatography and identified as cubilin, the recently described intrinsic factor-vitamin B 12 . Cubilin antibodies inhibit endocytosis in mouse embryo endoderm, a prominent site of cubilin expression. Cubilin-mediated is inhibitable 2 , 3 apolipoprotein (apo)A-I, apoA-II, apoE, RAP, but not...
Increased arginase activity contributes to endothelial dysfunction by competition for l-arginine substrate and reciprocal regulation of nitric oxide synthase (NOS). The rapid increase in human aortic cells exposed oxidized low-density lipoprotein (OxLDL) is consistent with post-translational modification or subcellular trafficking.To test the hypotheses that OxLDL triggers reverse translocation mitochondrial 2 (Arg2) cytosol Arg2 activation, this process dependent on processing peptidase,...
Apolipoprotein CII is an obligatory activator of lipoprotein lipase. Human patients with APOC2 deficiency display severe hypertriglyceridemia while consuming a normal diet, often manifesting xanthomas, lipemia retinalis and pancreatitis. Hypertriglyceridemia also important risk factor for development cardiovascular disease. Animal models to study are limited, no Apoc2 knockout mouse reported. To develop genetic model hypertriglyceridemia, we generated apoc2 mutant zebrafish characterized by...
An apolipoprotein C-II peptide mimetic for the treatment of hypertriglyceridemia activates lipoprotein lipase and blocks C-III.
Psoriasis is a systemic inflammatory skin disease associated with cardiovascular and lipid dysfunction. However, traditional parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this driven condition may capture additional risk. Recently, study showed that psoriasis was increased lipid-rich coronary plaques; therefore, investigating potential relationships speed understanding of psoriasis.To understand whether associate phenotypes, cardiometabolic...
COVID-19 is a global pandemic currently in an acute phase of rapid expansion. While public health measures remain the most effective protection strategy at this stage, when peak passes, it will leave its wake important problems. Historically, very few viruses have ever been eradicated. Instead, virus may persist communities causing recurrent local outbreaks infection as well several chronic diseases that arise from presence "suppressed" or consequence initial exposure. An ideal solution...
Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Inhibitors proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator LDL-C metabolism, have emerged as promising approaches for reducing elevated levels. Here, we evaluated cholesterol-lowering efficacy virus-like particle (VLP) based vaccines that target epitopes found within LDL receptor (LDL-R) binding domain PCSK9. In...
BACKGROUND: Cholesterol efflux capacity (CEC) predicts cardiovascular disease independently of high-density lipoprotein (HDL) cholesterol levels. Isolated small HDL particles are potent promoters macrophage CEC by the ABCA1 (ATP-binding cassette transporter A1) pathway, but underlying mechanisms unclear. METHODS: We used model system studies reconstituted and plasma from control lecithin-cholesterol acyltransferase (LCAT)–deficient subjects to investigate relationships among sizes particles,...
Currently, there are high degrees of both enthusiasm and controversy regarding the potential diagnostic application matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry (1)(2)(3)(4)(5)(6)(7). This technique permits simultaneous analysis a large number polypeptide components in biological fluids. Greatest sensitivity resolution achieved by MALDI TOF range from ∼500 to 20 000 Da; this has led recognition that is highly complex mixture peptide serum circulate...
BACKGROUND : Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor management of associated symptoms have been critically evaluated during leukapheresis in healthy donors. STUDY DESIGN AND METHODS Symptom assessments (n = 315) and laboratory analyses 49) were 244 with 71 without prophylactic calcium (Ca) chloride or Ca gluconate given a dose linked to infusion rate...
The ATP binding cassette (ABC) half-transporters ABCG5 and ABCG8 facilitate biliary intestinal removal of neutral sterols. Here, we identify a site for the orphan nuclear receptor liver homolog-1 (LRH-1) at nt 134–142 ABCG5/ABCG8 intergenic region necessary activity both promoters. Mutating this LRH-1 reduced promoter human more than 7-fold in HepG2 Caco2 cells. Electrophoretic mobility shift assays with extracts demonstrated specific to motif region. overexpression increased up 1.6-fold...
Pulmonary hypertension (PH) in sickle cell disease (SCD) is an emerging and important clinical problem. In a single-institution adult cohort of 365 patients, we investigated lipid lipoprotein levels their relationship to markers intravascular haemolysis, vascular dysfunction PH. agreement with prior studies, confirm significantly decreased plasma total cholesterol, high-density lipoprotein-cholesterol (HDL-C) low-density (LDL-C) SCD versus ethnically-matched healthy controls. Several...
Background: Thioredoxin (TRX)-1, a ubiquitous 12-kDa protein, exerts antioxidant and anti-inflammatory effects. In contrast, the truncated form, called TRX80, produced by macrophages induces upregulation of proinflammatory cytokines. TRX80 also promotes differentiation mouse peritoneal human toward M1 phenotype. Methods: TRX1 plasma levels were determined with specific ELISA. A disintegrin metalloproteinase domain-containing protein (ADAM)-10, ADAM-17, ADAM-10 activities measured SensoLyte...