Preferred Label : LDL Pathway;
NCIt related terms : Low-density lipoprotein (LDL) pathway during atherogenesis;
Alternative definition : BIOCARTA: Low-density lipoprotein (LDL) is a plasma lipoprotein particle whose lipid
component includes cholesterol and triglycerides and is commonly referred to as bad
cholesterol due to its role promoting atherogenic heart disease. LDL in the plasma
originates from very-low density lipoprotein (vLDL) produced by the liver with the
apoprotein B-100. vLDL is converted to LDL by the action of lipoprotein lipase, an
enzyme that hydrolyzes triglycerides in vLDL, removing them from the vLDL particle
and releasing free fatty acids. The removal of triglycerides from vLDL by lipoprotein
lipase leaves a greater proportion of cholesterol, increasing the density of the particle
and changing it to LDL. Atherogenic heart disease involves the formation of plaques
in arterial walls that narrow the arterial passage, restricting blood flow and increasing
the risk of occlusion of blood flow by a myocardial infarction. One of the first steps
in the development of atherogenic heart disease is the passage of LDL out of the arterial
lumen and into the arterial wall. Once there, the lipids in LDL are chemically modified
and oxidized. Oxidized LDL stimulates inflammatory signaling by neighboring endothelial
cells, releasing chemokines and cytokines such as M-CSF and MCP-1 and recruiting monocytes
into the arterial wall. Once there, monocytes differentiate into macrophages and internalize
modified LDL. These macrophages continue to internalize LDL, becoming enlarged and
full of lipid. These cells accumulate in tissue and are transformed into foam cells,
dying and forming part of the atherogenic plaque. Therapeutic intervention in atherogenic
heart disease focuses first on lowering plasma LDL levels through diet and medication.
The statins are drugs commonly used to block cholesterol production and increase the
expression of the LDL receptor by the liver, removing LDL from circulation. Blocking
LDL oxidation may also protect against atherogenesis, and may be the mechanism by
which antioxidants such as vitamin E are proposed to reduce heart disease. Blocking
the uptake of LDL by macrophages or inhibiting the inflammatory reaction against modified
LDL may also offer routes to reduce the formation of atherogenic plaques. (This definition
may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_LDLpathway;
Origin ID : C39137;
UMLS CUI : C1517685;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
