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Hyperlipidemias and small dense LDLs in patients with high-triglyceride low-HDL syndromes lead to a prolonged half life of apoB-containing particles. This is associated with reactive oxygen species (ROS) activation and leads to formation of oxidized LDL (Ox-LDL). Generators of ROS in macrophages (MACs) include myeloperoxidase (MPO)-mediated respiratory(More)
Monocytes are precursors of macrophages. Here we demonstrate that macrophage colony-stimulating factor (M-CSF)-dependent differentiation of primary human monocytes from healthy volunteers induces transcription of SREBP-1c target genes required for fatty acid (FA) biosynthesis and impairs transcription of SREBP-2 target genes required for cholesterol(More)
Recruitment of circulating monocytes and formation of macrophage foam cells in the arterial intima are characteristic features of atherogenesis. Foam cells are formed by cellular uptake and storage of atherogenic lipoproteins, including oxidized LDL (oxLDL) and enzymatically modified LDL (eLDL). Dissection of oxLDL- and eLDL-induced cellular phenotypes(More)
The ATP-binding cassette transporter A1 (ABCA1) facilitates the cellular release of cholesterol and choline-phospholipids to apolipoprotein A-I (apoA-I) and several studies indicate that vesicular transport is associated with ABCA1 function. Syntaxins play a major role in vesicular fusion and have also been demonstrated to interact with members of the(More)
HDL functions mainly as a cholesterol scavenger, facilitating transport of cholesterol to the liver for conversion to bile acids and secretion into the bile for elimination or recycling in the enterohepatic bile acid cycle. Because of its major function in cholesterol clearance, HDL is in general considered to be atheroprotective. From cell cholesterol can(More)
The highly homologous genes NIPSNAP3 and NIPSNAP4, with 87% amino acid identity, are members of the NIPSNAP family with putative roles in vesicular trafficking. NIPSNAP3 mRNA and NIPSNAP4 mRNA and protein were detected in multiple tissues and cells at varying degrees. Interestingly, NIPSNAP3 is most highly expressed in skeletal muscle, where NIPSNAP4 has a(More)
This review summarizes the current knowledge of endolysosomal and cytoplasmic lipid storage in macrophages induced by oxidized LDL (Ox-LDL), enzymatically degraded LDL (E-LDL) and other atherogenic lipoprotein modifications, and their relation to the adapter protein 3 (AP-3) dependent ABCA1 and ABCG1 cellular lipid efflux pathways. We compare endolysosomal(More)
PURPOSE OF REVIEW Lipid membrane microdomains are involved in major types of disease, ranging from vascular and metabolic diseases to neurodegeneration, autoimmunity, infectious and inflammatory diseases, and cancer. This review provides an update of membrane microdomain abnormalities. RECENT FINDINGS Lipid membrane microdomains are dynamic assemblies of(More)
Atherosclerosis is characterized by the generation of lipid-loaded macrophage-derived foam cells. To study the effect of different types of atherogenic lipoproteins, human macrophages were loaded with enzymatically degraded low density lipoprotein (E-LDL) or oxidized LDL (Ox-LDL). Cellular cholesterol content was increased by E-LDL, whereas Ox-LDL increased(More)
BACKGROUND The analysis of high-throughput gene expression data sets derived from microarray experiments still is a field of extensive investigation. Although new approaches and algorithms are published continuously, mostly conventional methods like hierarchical clustering algorithms or variance analysis tools are used. Here we take a closer look at(More)