low-density lipoprotein particle remodeling

Definition

Target type: biologicalprocess

The acquisition, loss or modification of a protein or lipid within a low-density lipoprotein particle, including the hydrolysis of triglyceride by hepatic lipase, with the subsequent loss of free fatty acid, and the transfer of cholesterol esters from LDL to a triglyceride-rich lipoprotein particle by cholesteryl ester transfer protein (CETP), with the simultaneous transfer of triglyceride to LDL. [GOC:BHF, GOC:expert_pt, GOC:mah, GOC:rl]

Low-density lipoprotein (LDL) particle remodeling is a complex process involving modifications to the structure and composition of LDL particles, influencing their biological activity and ultimately their role in cardiovascular disease. Here's a detailed description:

**1. Initial LDL Formation:** LDL particles are formed in the liver and other tissues from very-low-density lipoprotein (VLDL) particles through a process called lipolysis. During lipolysis, triglycerides in VLDL are hydrolyzed, releasing free fatty acids and leaving behind smaller, denser particles known as LDL.

**2. Oxidation:** One of the key events in LDL remodeling is oxidation. Reactive oxygen species (ROS) can attack LDL particles, causing modifications to their lipid and protein components. Specifically, oxidation targets the polyunsaturated fatty acids in LDL, leading to the formation of lipid hydroperoxides and other oxidized products. These modifications alter the chemical structure and conformation of the LDL molecule.

**3. Modification of ApoB-100:** LDL particles contain a protein called apolipoprotein B-100 (ApoB-100), which plays a role in receptor binding and lipid transport. Oxidation can modify ApoB-100, leading to the formation of oxidized lipid adducts. These modifications can alter the interaction of LDL with cellular receptors, potentially reducing its uptake by cells.

**4. Formation of Scavenger Receptor Binding Sites:** Oxidation of LDL can create sites that are recognized by scavenger receptors on macrophages. These receptors are not as selective as the classical LDL receptor and can bind to a wide range of modified LDL particles, including oxidized LDL.

**5. Foam Cell Formation:** When macrophages bind to oxidized LDL via scavenger receptors, they internalize the modified particles. This leads to the accumulation of cholesterol esters within the macrophage, eventually transforming it into a foam cell. Foam cells are characteristic of atherosclerotic plaques, which are the underlying cause of heart disease.

**6. Inflammation and Atherosclerosis:** The accumulation of oxidized LDL and foam cells in blood vessels promotes inflammation and contributes to the development of atherosclerosis. Inflammatory cells release cytokines and chemokines, further contributing to the growth and progression of plaque formation.

**7. Other Modifications:** Besides oxidation, LDL particles can undergo other modifications, including glycation and enzymatic modifications. These modifications can also alter the structure and function of LDL, impacting its biological activity.

In summary, LDL particle remodeling, particularly through oxidation, plays a central role in cardiovascular disease by modifying the structure, composition, and function of LDL particles. These changes influence their uptake by cells, their interaction with receptors, and their ability to promote inflammation and atherogenesis.'
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Proteins (11)

Compounds (129)