A5071671502- Vitamin D Research Studies
- Atherosclerosis and Cardiovascular Diseases
- Lipid metabolism and disorders
- Animal Nutrition and Physiology
- Cancer, Lipids, and Metabolism
- Apelin-related biomedical research
- Trace Elements in Health
- Calcium signaling and nucleotide metabolism
- Galectins and Cancer Biology
- Lysosomal Storage Disorders Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Ion channel regulation and function
- Metabolism, Diabetes, and Cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Adenosine and Purinergic Signaling
- Biotin and Related Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiac Fibrosis and Remodeling
- Vitamin C and Antioxidants Research
- Sulfur Compounds in Biology
- Lipid Membrane Structure and Behavior
- Biomarkers in Disease Mechanisms
- Protein Tyrosine Phosphatases
- Growth Hormone and Insulin-like Growth Factors
Washington University in St. Louis
2004-2024
Universidad Nacional de Córdoba
1996-2011
Here we show a unique example of male infertility conferred by gene knockout the sperm‐specific, pH‐dependent SLO3 potassium channel. In striking contrast to wild‐type sperm which undergo membrane hyperpolarization during capacitation, found that mutant depolarization. Several defects in are evident under capacitating conditions, including impaired motility, bent “hairpin” shape, and failure acrosome reaction (AR). The AR is rescued valinomycin hyperpolarizes sperm. Thus principal channel...
Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted and therapeutic target for reducing plasma triglyceride-rich lipoproteins (TRL) low-density lipoprotein cholesterol (LDL). Although ANGPTL3 modulates the metabolism of circulating lipoproteins, its role in TRL assembly secretion remains unknown. CRISPR-associated 9 (CRISPR/Cas9) was used to HepG2 cells (ANGPTL3-/-) whereupon we observed ∼50% reduction ApoB100 secretion, accompanied by an increase early presecretory degradation...
Reducing SVEP1 confers protection from atherosclerosis and may be a therapeutic target for the treatment prevention of coronary artery disease.
Abstract Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease associates with platelet reactivity in humans. Here, using a human genomic proteomic approach, we identify high affinity, disease-relevant, potentially targetable interaction between SVEP1 the orphan receptor Platelet Endothelial Aggregation Receptor (PEAR1). This PEAR1 phosphorylation associated AKT/mTOR signaling cells...
LIPA (lysosomal acid lipase) mediates cholesteryl ester hydrolysis, and patients with rare loss-of-function mutations develop hypercholesterolemia severe disease. Genome-wide association studies of coronary artery disease have identified several tightly linked, common intronic risk variants in which unexpectedly associate increased mRNA expression. However, an exonic variant (rs1051338 resulting T16P) linkage lies the signal peptide region putatively disrupts trafficking. We sought to...
A structure has been proposed for glucose transporter-1 (GLUT1) based upon homology modeling that is consistent with the results of numerous mutagenesis studies (Mueckler, M., and Makepeace, C. (2004) J. Biol. Chem. 279, 10494–10499). To further test refine this model, relative orientation proximity transmembrane helices 4 8 were analyzed by chemical crosslinking di-cysteine mutants created in a reporter GLUT1 construct. All six native cysteine residues changed to either glycine or serine...
Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most disease-associated lie within non-coding regions the genome, rendering it difficult to determine downstream causal gene and cell type. Here, we performed paired single nucleus expression chromatin accessibility profiling from 44 human arteries. To link molecular traits, developed a meta-map 88 samples discovered...
Abstract Vitamin D deficiency affects the lipid composition and Ca2+ uptake of intestinal basolateral membranes from chick intestine. The increased cholesterol content causes an increase in molar ratio cholesterol/phospholipid. Phospholipid classes remain unchanged, but percentages arachidonic acid major phospholipid fractions are increased. After 24 hours oral administration 2,000 IU cholecalciferol to vitamin D‐deficient chicks, values do not change, amount returns normal values. driven by...
Rationale: Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted and therapeutic target for reducing plasma triglyceride-rich lipoproteins low-density lipoprotein cholesterol (LDL). Although ANGPTL3 modulates lipolytic pathways in the metabolism of circulating lipoproteins, its potential hepatocyte-specific role very (VLDL) assembly secretion remains unknown. Methods: We established hepatocyte cell culture systems, including CRISPR/Cas9-edited “knock out” (KO) HepG2 cells isogenic...
Two tightly linked common intronic variants at the LIPA locus (which encodes for Lysosomal Acid Lipase - LAL) are present in nearly one-third of population and known to increase risk coronary artery disease (CAD) by 13-17% large-scale genome-wide association studies. LAL mediates hydrolysis cholesteryl esters patients with rare loss-of-function mutations develop hypercholesterolemia CAD. However, these non-coding, not associated lipid abnormalities, result increased transcripts monocytes, a...
Summary A low-frequency variant of SVEP1, an extracellular matrix protein, is associated with risk coronary disease in humans independent plasma lipids. Despite a robust statistical association, however, it was unclear if and how SVEP1 might contribute to atherosclerosis. Here, using Mendelian randomization complementary mouse models, we provide evidence that promotes atherosclerosis mice. We find expressed by vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque. VSMCs also...
Background: Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that circulates in plasma causally related to cardiovascular disease, hypertension, 2 diabetes. A recent genome wide association study (GWAS) also implicates SVEP1 platelet reactivity. The gene most strongly associated with reactivity the GWAS Platelet Endothelial Cell Receptor ( PEAR1 ), a encodes orphan receptor tyrosine kinase-like associates disease. Little...