A5029146873- Lipoproteins and Cardiovascular Health
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Atherosclerosis and Cardiovascular Diseases
- Drug Transport and Resistance Mechanisms
- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Inflammatory mediators and NSAID effects
- Nuclear Receptors and Signaling
- Retinoids in leukemia and cellular processes
- RNA modifications and cancer
- Pancreatic function and diabetes
- Lipid metabolism and disorders
- Nitric Oxide and Endothelin Effects
- Advanced Proteomics Techniques and Applications
- Systemic Lupus Erythematosus Research
- Caveolin-1 and cellular processes
- Sphingolipid Metabolism and Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Protease and Inhibitor Mechanisms
- Congenital heart defects research
- Glycosylation and Glycoproteins Research
- Protein Kinase Regulation and GTPase Signaling
- Tissue Engineering and Regenerative Medicine
National Institutes of Health
2018-2023
National Heart Lung and Blood Institute
2018-2023
AstraZeneca (United States)
2019-2023
Jacksonville Center for Clinical Research
2021
Bioscience Research
2021
Stavros Niarchos Foundation
2018
University of Maryland, Baltimore
2016-2017
Eli Lilly (United States)
2005-2011
AstraZeneca (Sweden)
2010
Pfizer (United States)
2001-2006
Apolipoprotein AI (apoAI) is a lipid-binding protein that participates in the transport of cholesterol and other lipids plasma. A complementary DNA clone for bound to regulatory elements apoAI gene was isolated. This protein, designated protein-1 (ARP-1), novel member steroid hormone receptor superfamily. ARP-1 as dimer, its dimerization domain localized COOH-terminal region. also thyroid hormone-responsive element regions apoB, apoCIII, insulin, ovalbumin genes. In cotransfection...
The human apo-E gene has been isolated from a X phage library using as probe the previously reported cDNA clone pE-301.X was mapped and subcloned, completely sequenced.The DNA sequence compared with that of near full length pE-368 revealed three introns.The first intron in region corresponds to 5' untranslated mRNA.The second interrupted codon specifying amino acid -4 signal peptide.The third 61 mature protein.Analysis four Alu sequences.Two were opposite orientations intron, one each...
The current coronavirus disease 2019 (COVID-19) pandemic presents a global challenge for managing acutely ill patients and complications from viral infection. Systemic inflammation accompanied by "cytokine storm," hemostasis alterations severe vasculitis have all been reported to occur with COVID-19, emerging evidence suggests that dysregulation of lipid transport may contribute some these complications. Here, we aim summarize the understanding potential mechanisms related COVID-19...
Rats and mice have two, equally expressed, nonallelic genes encoding preproinsulin (genes I II). Cytological hybridization with metaphase chromosomes indicated that both reside on rat chromosome but are approximately 100,000 kilobases apart. In the two different chromosomes. DNA sequence comparisons of gene-flanking regions in rats gene has lost one introns present II, is flanked by a long (41-base) direct repeat, remnant polydeoxyadenylate acid tract preceding downstream repeat. These...
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that regulates low density lipoprotein receptor (LDLR) protein levels. The mechanisms of this action, however, remain to be defined. We show here recombinant human PCSK9 expressed in HEK293 cells was readily secreted into the medium, with prosegment associated C-terminal domain. Secreted mediated cell surface LDLR degradation concentration- and time-dependent manner when added cells. Accordingly, cellular LDL uptake...
In clinical studies, sphingomyelin (SM) plasma levels correlated with the occurrence of coronary heart disease independently cholesterol levels. We hypothesized that inhibition SM synthesis would have antiatherogenic effects. To test this hypothesis, apolipoprotein E (apoE)-knockout (KO) mice were treated myriocin, a potent inhibitor serine palmitoyltransferase, rate-limiting enzyme in biosynthesis.Diet-admix treatment apoE-KO myriocin Western diet for 12 weeks lowered and sphinganine...
Decreased plasma high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I levels have been associated with premature coronary artery disease. We identified a PstI restriction-endonuclease site flanking the human gene at its 3' end that is polymorphic. The absence presence of this site, as determined by genomic blotting analysis PstI-digested chromosomal DNA use an probe, were 3.3-kb 2.2-kb hybridization bands, respectively. band appeared in 4.1 percent 123 randomly selected control...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDistribution of apolipoprotein A-I, C-II, C-III, and E mRNA in fetal human tissues. Time-dependent induction by cultures monocyte-macrophagesVassilis I. Zannis, F. Session Cole, Cynthia L. Jackson, David M. Kurnit, Sotirios K. KarathanasisCite this: Biochemistry 1985, 24, 16, 4450–4455Publication Date (Print):July 30, 1985Publication History Published online1 May 2002Published inissue 30 July...
Northern blotting analysis has shown apo-E mRNA synthesis by human liver, HepG2 cells, and primary cultures of monocyte macrophages but not the macrophage-like cell line U937 normal or transformed fibroblasts. Cell-free translation that product consists one major minor isoprotein apparent Mr = 28,500 isoelectric points 6.20 6.02, respectively. These isoproteins differ +1 0 charges from apo-E3 have been designated preapo-E. Co-translational treatment with dog pancreatic membranes converts...
We have isolated cDNA clones encoding human apolipoprotein (apo) A-I. Twenty putative apo A-I were selected by screening 10,000 of an adult liver library with oligonucleotide probe. The probe was a mixture synthetic 14-base-long DNA oligomers constructed to correspond the codons for amino acids 105-109. Four these examined further and showed 600- 800-base-pair (bp) inserts. Preliminary restriction mapping partial sequence analysis indicated that shorter inserts subset longer clone insert...
Cardiac progenitor cells are an attractive cell type for tissue regeneration, but their mechanism myocardial remodeling is still unclear.This investigation determines how chronological age influences the phenotypic characteristics and secretome of human cardiac (CPCs), potential to recover injured myocardium.Adult (aCPCs) neonatal (nCPCs) were derived from patients aged >40 years or <1 month, respectively, functional was determined in a rodent infarction model. A more robust vitro...
The genes coding for apolipoproteins (apo) AI, CIII, and AIV, designated APOA1, APOC3, APOA4, respectively, are closely linked tandemly organized in the long arm of human chromosome 11. A DNA rearrangement involving encoding apoAI apoCIII certain patients with premature atherosclerosis has been associated deficiency both plasma these patients. Structural characterization one indicates that this consists a inversion containing portions 3' ends genes, including region between genes....
We have recently proposed that the major secreted isoprotein form of human apolipoprotein A-I (designated apo A-I2) is modified extracellularly to become predominant seen in plasma A-I4). In current report we demonstrate primary translation product A-I2p) has a 24-amino-acid NH2-terminal extension with sequence Met-Lys-Ala-Ala-Val-Leu-Thr-Leu-Ala-Val-Leu-Phe- Leu-Thr-Gly-Ser-Gln-Ala-Arg-His-Phe-Trp-Gln-Gln. The first 18 amino acids this are cleaved intracellularly by signal peptidase,...
Functional interactions or cross-talk between ligand-activated nuclear receptors and the proinflammatory transcription factor factor-kappaB (NF-kappaB) may play a major role in ligand-mediated modification of diseases processes. In particular, cardioprotective effects estrogen replacement therapy are thought to be due part ability ligand-bound receptor (ER) inhibit NF-kappaB function. current study 17beta-estradiol-bound ERalpha interfered with cytokine-induced activation reporter HepG2...
Cholesteryl ester transfer protein (CETP) catalyses the exchange of cholesteryl and triglyceride between HDL apoB containing lipoprotein particles. The role CETP in modulating plasma cholesterol levels humans is well established there have been significant efforts to develop inhibitors increase for treatment coronary artery disease. These efforts, however, hampered by fact that most either low potency or undesirable side effects. In this study, we describe a novel benzazepine compound...
The genes for two of the apolipoproteins, apo A-I and C-III, previously shown to be within 3kb in genome, were localized human chromosome 11 by Southern blot analysis DNA from human-rodent somatic cell hybrids. These exhibit polymorphisms associated with dyslipoproteinemia premature atherosclerosis, it will now possible examine relationship these many others that have been assigned this chromosome.
cDNA clones encoding human apolipoprotein E were identified by screening an adult liver library with oligonucleotide probe. The probe was a mixture of synthetic 14-base long DNA oligomers constructed to correspond all possible codons for apo-E amino acids 218-222. Plasmids from four the 20 selected this procedure digested PstI and had five internal sites total length insert approximately 900 base pairs. sequence analysis one these clones, designated pE-301, revealed that it corresponded...
We assessed secondary and genetic causes of severe HDL deficiency in 258,252 subjects, whom 370 men (0.33%) 144 women (0.099%) had cholesterol levels <20 mg/dl. excluded 206 subjects (40.1%) with significant elevations triglycerides, C-reactive protein, glycosylated hemoglobin, myeloperoxidase, or liver enzymes receiving testosterone. sequenced 23 lipid-related genes 201 (65.3%) 308 eligible subjects. Mutations (23 novel) selected variants were found at the following gene loci: 1) ABCA1...
The estrogen receptor (ER) belongs to a superfamily of ligand-inducible transcription factors. Functions these proteins (dimerization, DNA binding, and interaction with other factors) are modulated by binding their corresponding ligands. It is, however, controversial whether various ER ligands affect the receptor's ability bind its specific element (ERE).By using real time analysis we have investigated kinetics human (h)ER in absence presence 17β-estradiol, 17α-ethynyl estradiol, analogs...