A5049870943- Cholesterol and Lipid Metabolism
- HIV-related health complications and treatments
- Diabetes, Cardiovascular Risks, and Lipoproteins
- HIV Research and Treatment
- Lipoproteins and Cardiovascular Health
- Peroxisome Proliferator-Activated Receptors
- Drug Transport and Resistance Mechanisms
- Lipid metabolism and biosynthesis
- Extracellular vesicles in disease
- Systemic Lupus Erythematosus Research
- HIV/AIDS drug development and treatment
- Reproductive System and Pregnancy
- Lipid metabolism and disorders
- Cancer, Lipids, and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Pancreatitis Pathology and Treatment
- Sphingolipid Metabolism and Signaling
- Nanopore and Nanochannel Transport Studies
- Lipid Membrane Structure and Behavior
- Cytomegalovirus and herpesvirus research
- Pain Mechanisms and Treatments
- interferon and immune responses
- Immune Response and Inflammation
- Immune cells in cancer
- Pancreatic function and diabetes
Baker Heart and Diabetes Institute
2011-2020
HIV infection has a profound effect on "bystander" cells causing metabolic co-morbidities. This may be mediated by exosomes secreted HIV-infected and containing viral factors. Here we show that HIV-1 protein Nef (exNef) are rapidly taken up macrophages releasing into the cell interior. caused down-regulation of ABCA1, reduction cholesterol efflux sharp elevation abundance lipid rafts through reduced activation small GTPase Cdc42 decreased actin polymerization. Changes in led to...
Apolipoprotein A-I binding protein (AIBP) reduces lipid raft abundance by augmenting the removal of excess cholesterol from plasma membrane. Here, we report that AIBP prevents and reverses processes associated with neuroinflammatory-mediated spinal nociceptive processing. The mechanism involves to Toll-like receptor-4 (TLR4) increased activated microglia, which mediates selective regulation rafts in inflammatory cells. AIBP-mediated reductions downregulate LPS-induced TLR4 dimerization,...
Cholesterol content of cells must be maintained within the very tight limits, too much or little cholesterol in a cell results disruption cellular membranes, apoptosis and necrosis 1. Cells can source from intracellular synthesis plasma lipoproteins, both sources are sufficient to fully satisfy cells' requirements for cholesterol. The processes uptake tightly regulated deficiencies rare 2. Excessive is more common problem 3. With exception hepatocytes some degree adrenocortical cells, unable...
Infusion of reconstituted HDL (rHDL) leads to changes in metabolism as well an increased capacity plasma support cholesterol efflux providing opportunity investigate mechanisms linking HDL. Patient plasmas after infusion rHDL were tested ex vivo for their stimulate efflux. Reconstituted enhanced mobilization from tissues shown by rising concentrations over the period. led vivo; surprisingly, removing apoB-containing lipoproteins while preserving all subfractions eliminated this increase....
Cytomegalovirus (HCMV) contains cholesterol, but how HCMV interacts with host cholesterol metabolism is unknown. We found that, in human fibroblasts, infection increased the efflux of cellular despite reducing abundance ABCA1. Mechanistically, viral protein US28 was acting through CDC42, rearranging actin microfilaments, causing association lipid rafts, and leading to a dramatic change and/or structure rafts. These changes displaced ABCA1 from cell surface created new binding sites for...
Atherosclerosis is an inflammatory disease associated with the activation of innate immune TLRs and nucleotide‐binding oligomerization domain‐containing protein (NOD)‐like receptor pathways. However, function most receptors in atherosclerosis remains unclear. Here, we show that NOD2 a crucial influencing vascular inflammation severity. 10‐week stimulation muramyl dipeptide (MDP), cognate ligand, aggravated atherosclerosis, as indicated by augmented lesion burden, increased enlarged...
Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities free their membrane, an important reverse transport. However, the exact RBCs systemic metabolism is poorly understood. were incubated with autologous plasma or isolated lipoproteins resulting significant net amount moved HDL, while LDL opposite direction. Furthermore, bi-directional between was saturable temperature-,...
The recent failures of HDL-raising therapies have underscored our incomplete understanding HDL biology. Therefore there is an urgent need to comprehensively investigate metabolism enable the development effective HDL-centric therapies. To identify novel regulators metabolism, we performed a joint analysis human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data identified association between trafficking protein, kinesin binding 2 (TRAK2) HDL-C concentration. Here...
HIV infection is known to be associated with cardiometabolic abnormalities; here we investigated the progression and causes of these abnormalities. Three groups participants were recruited: HIV-negative subjects two treatment-naïve HIV-positive subjects, one group initiating antiretroviral treatment, other remaining untreated. Intima-media thickness (cIMT) increased in untreated compared group, but treatment mitigated difference. We found no increase diabetes-related metabolic markers or...
HIV-associated neurocognitive disorders (HANDs) are a frequent outcome of HIV infection. Effective treatment infection has reduced the rate progression and severity but not overall prevalence HANDs, suggesting ongoing pathological process even when viral replication is suppressed. In this study, we investigated how HIV-1 protein Nef secreted in extracellular vesicles (exNef) impairs neuronal functionality. ExNef were rapidly taken up by neural cells vitro, reducing abundance ABC transporter...
AIBP (apolipoprotein A-I binding protein) is an effective and selective regulator of lipid rafts modulating many metabolic pathways originating from the rafts, including inflammation. The mechanism action was suggested to involve stimulation by cholesterol efflux, depleting cholesterol, which essential for raft integrity. Here we describe a different contributing regulation AIBP. Approach Results: We demonstrate that modulation may not exclusively depend on rate efflux or presence key ABCA1...
Objective To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers lipids to investigate their relationship with subclinical atherosclerosis in a cohort treatment-naive HIV-infected patients. Methods We performed prospective, comparative, multicenter study 2 groups patients (group A, CD4>500 cells/μL, not starting c-ART; group B, CD4<500 c-ART at baseline) healthy control group. Laboratory analyses carotid ultrasound were baseline...
Serum amyloid A (SAA), which is one of the acute phase proteins, alters structure HDL by associating with it during circulation. We focused on whether SAA influences values HDL-cholesterol (HDL-C) measurements when using a homogeneous assay.HDLs were isolated ultracentrifugation from serum samples 248 patients that stratified into three groups based their concentrations (low: ≤ 8 μg/mL; middle: < 100 and high: > μg/mL). HDL-C measured assay compared total cholesterol fractions...
Lipid rafts are distinct liquid-ordered domains of plasma membranes most eukaryotic cells providing platform for signaling pathways. composition is critical their structural integrity and regulation pathways originating from rafts. Here we provide a protocol to isolate lipid cultured human animal comprehensively analyse composition.
Previous in vitro and vivo studies demonstrated that HIV protein nef plays a key role impairing cellular systemic cholesterol metabolism disease, but clinical support for these findings is lacking. Here we present the data of comparative lipidomic analysis (330 lipid species) plasma samples from HIV-negative subjects, patients infected with WT HIV-1 strain nef-deficient HIV-1. We determine which effects on lipidome are explained by presence nef. The can be used to evaluate cardiovascular...