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Plasma lipid transfer proteins
1Department of Medicine, Columbia University, New York, New York 10032, USA.
Insights
Cholesteryl ester transfer protein (CETP) facilitates lipid exchange between lipoproteins, playing a key role in reverse cholesterol transport. Despite lowering HDL, CETP exhibits anti-atherogenic effects by moving cholesterol to the liver.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Plasma lipid transfer proteins facilitate the exchange of phospholipids and neutral lipids among lipoproteins.
- Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) belong to the lipid transfer/lipopolysaccharide binding gene family.
- CETP possesses binding sites for cholesteryl esters and triglycerides, operating via a carrier-mediated mechanism.
Purpose of the Study:
- To elucidate the role of Cholesteryl Ester Transfer Protein (CETP) in lipid metabolism and reverse cholesterol transport.
- To understand the impact of CETP on High-Density Lipoprotein (HDL) metabolism.
- To investigate the relationship between CETP activity and atherosclerosis.
Main Methods:
- Analysis of CETP's molecular structure and function, including its binding sites.
- Investigation of CETP's role in the catabolism of HDL cholesteryl esters.
- Examination of CETP gene expression regulation in response to dietary cholesterol and hypercholesterolemia.
Main Results:
- CETP mediates the catabolism of HDL cholesteryl esters, leading to reduced HDL size and protein content.
- CETP is central to reverse cholesterol transport, facilitating cholesterol movement from the periphery to the liver.
- CETP gene expression increases with elevated dietary cholesterol or endogenous hypercholesterolemia.
Conclusions:
- CETP plays a critical role in the dynamic exchange of lipids within plasma lipoproteins.
- Despite reducing HDL levels, CETP's function in reverse cholesterol transport suggests a protective effect against atherosclerosis.
- Understanding CETP's mechanisms is crucial for developing strategies to manage cardiovascular disease.
Abstract:
The plasma lipid transfer proteins mediate the transfer and exchange of phospholipids and neutral lipids between the plasma lipoproteins. The cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) are members of the lipid transfer/lipopolysaccharide binding gene family. The CETP contains binding sites for cholesteryl ester and triglycerides and probably acts by a carrier-mediated mechanism. The CETP mediates catabolism of HDL cholesteryl esters, with secondary decreases in HDL size and protein content. The CETP plays a central role in reverse cholesterol transport i.e. the centripetal movement of cholesterol from the periphery back to the liver. CETP gene expression is upregulated in response to increased dietary cholesterol or endogenous hypercholesterolemia. Although CETP reduces HDL levels, its role in reverse cholesterol transport suggests a dominant anti-atherogenic action in vivo.