Lipid transfer proteins: past, present and perspectives.

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Inflammation Biology

Background:

• Lipid transfer proteins, including PLTP and CETP, influence cholesterol levels in arteries, impacting atherosclerosis.
• Endotoxins disrupt reverse cholesterol transport (RCT), highlighting a pro-inflammatory role for HDL in conditions with premature atherosclerosis.
• Existing research presents conflicting findings on PLTP and CETP roles in atherosclerosis and acute inflammation.

Purpose of the Study:

• To elucidate the complex and seemingly contradictory roles of PLTP and CETP in atherogenesis and acute inflammation.
• To highlight the importance of understanding these roles for developing effective atherosclerosis prevention strategies.

Main Methods:

• Review of clinical studies and experimental animal models investigating PLTP and CETP in relation to atherosclerosis.
• Analysis of endotoxin-induced inflammation models and their impact on RCT.
• Examination of human population studies and experimental endotoxemia data.

Main Results:

• High PLTP activity is linked to atherosclerosis, but its effects are confounded by HDL-C lowering and inflammatory changes.
• CETP inhibition appears atheroprotective by reducing apoB-lipoprotein-cholesterol, despite facilitating HDL-C mediated RCT.
• Experimental CETP expression can protect against endotoxin-induced harm, and reduced CETP correlates with lower mortality in sepsis patients.

Conclusions:

• The biological functions of PLTP and CETP in atherosclerosis and acute inflammation present a complex picture with contradictory evidence.
• Careful monitoring of PLTP and CETP activity is crucial when developing drugs that inhibit these proteins for atherosclerosis prevention.