high-density lipoprotein particle remodeling

Definition

Target type: biologicalprocess

The acquisition, loss or modification of a protein or lipid within a high-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]

High-density lipoprotein (HDL) particle remodeling is a dynamic process involving changes in the size, composition, and structure of HDL particles, contributing to their diverse functions in lipid metabolism and reverse cholesterol transport (RCT). This process involves a series of enzymatic reactions and interactions with other lipoproteins and cells, ultimately influencing the efficiency of cholesterol removal from peripheral tissues and delivery to the liver.

**Initial Formation and Composition:**

HDL particles are initially assembled in the liver and intestines as nascent HDL (pre-beta HDL) particles. These nascent particles are small and have a high content of apolipoprotein A-I (apoA-I), a major structural protein of HDL. They also contain small amounts of other lipids, such as cholesterol esters (CE) and phospholipids.

**Enzymatic Modifications and Lipid Exchange:**

Nascent HDL particles undergo enzymatic modifications and lipid exchange interactions with other lipoproteins and cells. These modifications contribute to the maturation of HDL particles and their ability to acquire cholesterol from peripheral tissues.

* **Lecithin:cholesterol acyltransferase (LCAT):** LCAT is an enzyme that catalyzes the esterification of cholesterol in HDL particles. This reaction converts free cholesterol to CE, which increases the capacity of HDL to carry cholesterol. LCAT activity is enhanced by apoA-I and requires the presence of phospholipids.

* **Cholesterol ester transfer protein (CETP):** CETP mediates the transfer of CE from HDL to other lipoproteins, such as very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). This transfer process is important for the delivery of cholesterol to tissues and contributes to the removal of cholesterol from HDL.

* **Phospholipid transfer protein (PLTP):** PLTP facilitates the exchange of phospholipids between HDL and other lipoproteins. This exchange process contributes to the formation of mature HDL particles with optimal lipid composition.

* **Lipoprotein lipase (LPL):** LPL hydrolyzes triglycerides (TG) in VLDL and chylomicrons, releasing free fatty acids. These fatty acids can be taken up by HDL particles, contributing to the formation of larger, more mature HDL particles.

**Cholesterol Acquisition and Reverse Cholesterol Transport:**

Mature HDL particles, now enriched in CE, have the capacity to acquire cholesterol from peripheral tissues. This process is crucial for RCT, the pathway responsible for removing cholesterol from the body.

* **Apolipoprotein A-I (apoA-I):** ApoA-I plays a key role in mediating the interaction of HDL with cell membranes. It binds to scavenger receptor class B type 1 (SR-BI), a receptor on the surface of cells, facilitating cholesterol efflux.

* **ABCA1:** ABCA1 is a transporter protein expressed in the liver, intestines, and other tissues. It promotes the efflux of free cholesterol from cells to HDL particles.

* **ATP-binding cassette transporter G1 (ABCG1):** ABCG1 is another transporter protein that contributes to cholesterol efflux from cells to HDL. It preferentially transports cholesterol esters.

**Delivery to the Liver and Excretion:**

HDL particles carrying cholesterol eventually deliver their cargo to the liver.

* **Hepatic lipase (HL):** HL hydrolyzes CE in HDL particles, releasing free cholesterol.

* **SR-BI:** HDL particles interact with SR-BI on the surface of hepatocytes, leading to the delivery of cholesterol to the liver.

* **Bile acid synthesis:** Cholesterol delivered to the liver can be converted into bile acids, which are excreted in the feces.

**Factors Influencing HDL Remodeling:**

Several factors can influence HDL remodeling, including:

* **Genetics:** Polymorphisms in genes encoding apoA-I, LCAT, CETP, and other proteins involved in HDL metabolism can affect HDL particle size and composition.

* **Lifestyle factors:** Diet, exercise, smoking, and alcohol consumption can influence HDL levels and remodeling.

* **Disease states:** Conditions such as diabetes, hyperlipidemia, and cardiovascular disease can disrupt HDL remodeling.

**Clinical Significance:**

HDL remodeling is a crucial process in maintaining lipid homeostasis and preventing atherosclerosis. Disruptions in HDL remodeling can lead to increased cholesterol levels, reduced RCT, and an elevated risk of cardiovascular disease. Understanding the complex mechanisms of HDL remodeling is essential for developing strategies to target HDL metabolism and improve cardiovascular health.'
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Proteins (8)

Compounds (25)