LCAT- targeted therapies: Progress, failures and future.

Area of Science:

• Biochemistry
• Cardiovascular Research
• Metabolic Disorders

Background:

• Lecithin: cholesterol acyltransferase (LCAT) is the sole plasma enzyme responsible for cholesterol esterification.
• LCAT activity is intrinsically linked to high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT).
• Dysfunctional LCAT contributes to familial LCAT deficiency (FLD) and fish eye disease (FED).

Purpose of the Study:

• To review the role of LCAT in HDL metabolism and RCT.
• To explore LCAT-targeted therapies for cardiovascular diseases and LCAT deficiencies.
• To evaluate LCAT as a potential therapeutic target for coronary heart disease and atherosclerosis.

Main Methods:

• Review of existing animal and clinical studies on LCAT.
• Analysis of therapeutic strategies including recombinant human LCAT (rhLCAT) injections, gene therapy, and small molecule activators.
• Discussion of ongoing clinical trials for rhLCAT therapies.

Main Results:

• LCAT plays a pivotal role in HDL metabolism and RCT.
• Various therapeutic approaches targeting LCAT have demonstrated promising outcomes.
• rhLCAT therapies have advanced to clinical phase II trials.

Conclusions:

• LCAT is a critical factor in lipid metabolism and cardiovascular health.
• Targeting LCAT offers potential therapeutic avenues for FLD, FED, and cardiovascular diseases.
• Further investigation into LCAT's mechanism may elucidate HDL heterogeneity and lipoprotein dynamics.