Specific characteristics of ELDL and OxLDL

Various modifications of LDL are known, including LDL modified by advanced glyca-tion end-products (AGE-LDL), myeloperoxidase-oxidized LDL (MPO-LDL), oxidized LDL (Ox-LDL), and enzymatically modified LDL (E-LDL). They differ in their uptake receptor-mediated recognition and endocytosis mechanisms and are delivered to lysosomes. In this review, especially E-LDL and Ox-LDL as two principal chemical modifications of LDL are described. Lipoprotein particles which are converted to proatherogenic...

Receptor entry pathways of modified LDL

Cellular internalization of LDL takes place via receptor-mediated endocytosis in a clathrin-dependent transport process (Fig. 3). This process begins at the cytosolic leaflet of the plasma membrane with the sequential assembly of coat components to form clathrin-coated pits. Lipid membrane microdomains and membrane lipid composition, especially membrane cholesterol content, are important in receptor-mediated endocytosis, and severe cholesterol depletion can inhibit clathrin-coated pit...

Cholesterol efflux from macrophages to prevent foam cell formation

The initial steps of reverse cholesterol transport involve export of cholesterol from peripheral cells to plasma lipoproteins for subsequent delivery to the liver. In vivo, HDL or its apolipoproteins act as acceptors of cholesterol from peripheral cells, carrying it to the liver for degradation. When cholesterol acceptors such as HDL are present, cholesterol efflux from macrophages is accelerated, which prevents foam cell formation. To produce this efflux, neutral cholesteryl ester hydrolase...

Endocannabinoid oxidation and its possible role

Due to the presence of an arachidonate moiety in their chemical structure, endocannabi-noids are in principle easily oxidized through the action of the same enzymes that catalyse the oxidation of arachidonic acid. Indeed, both anandamide and 2-AG are substrates for some enzymes of the arachidonate cascade, in particular the 12- and 15-lipoxygenases, cytochrome p450 oxygenases and COX-2 (Fig. 3). These reactions have been found to occur in intact cell systems only in a few cases, and never in...

Commonalities between anandamide and 2AG anabolic and catabolic reactions

A scenario is now emerging indicating that, although different endocannabinoids share the same molecular targets, their levels are regulated in entirely different ways. This seems to apply particularly to AEA and 2-AG, whose biosynthetic and degradative pathways are Fig. 2 Commonalities between anandamide and 2-arachidonoylglycerol metabolic pathways. A family of direct biosynthetic precursors, produced from phospholipid remodelling, are all converted into endocannabi-noids (R arachidonyl...

Macrophages and atherosclerosis

Atherosclerosis is a chronic vascular disease characterized by lipid retention and inflammation. As a result of disturbed lipid homeostasis, chronic remodeling, inflammation, and focal calcification or fibrosis accelerate atherogenesis. Innate immune recognition receptors such as charge and motif receptors or opsonin receptors such as Fcy and complement receptors which bind either antibodies and pentraxins, or complement, are involved in inflammatory activation during disease progression. In...

References

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Ac Erk Plc Pi3K

Fig. 3 Signaling pathways regulated by the LPA family of G-protein coupled receptors. Shown are the four known LPA receptors and the G proteins coupled to them. Cell signaling pathways downstream of receptor signaling are indicated. AC adenylyl cyclase, ERK mitogen-activated protein kinase, PLC phospholipase C, PI3K phosphoinositol 3-kinase and thickening of the developing cerebral cortex (Kingsbury et al. 2003). This remarkable morphological change is due to an LPA-dependent decrease in cell...

ABCA1interacting proteins and lipid membrane microdomains

The Rho family GTPase Cdc42 directly interacts with ABCA1 to control filopodia formation, actin organization, and intracellular lipid transport (Diederich et al. 2001 Tsukamoto et al. 2001). We have previously shown (Drobnik et al. 2002) that ABCA1 and Cdc42 were partially localized in Lubrol- but not in Triton-X DRMs and that apoA-I preferentially depleted unesterified cholesterol phospholipids from Lubrol DRMs, whereas HDL3 additionally decreased the cholesterol content of Triton-X DRMs. The...