Recent developments with lipoprotein-associated phospholipase A2 inhibitors
Ryan J Chauffe1, Robert L Wilensky, Emile R Mohler
1Pennsylvania Hospital, 1 Pine West, 800 Spruce Street, Philadelphia, PA 19107, USA. chauffer@uphs.upenn.edu
Current Atherosclerosis Reports
|April 29, 2010
Summary
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) promotes atherosclerosis by generating inflammatory mediators. Inhibiting Lp-PLA(2) shows therapeutic potential by reducing plaque development and vulnerability.
Area of Science:
- Cardiovascular Biology
- Enzymology
- Pharmacology
Background:
- Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an enzyme linked to atherosclerosis.
- Its role was debated, but evidence now supports a proatherogenic function.
Purpose of the Study:
- To review recent developments in selective Lp-PLA(2) inhibition as a therapeutic strategy.
- To highlight the role of Lp-PLA(2) in promoting atherosclerotic plaque vulnerability.
Main Methods:
- Review of recent animal models and human studies on Lp-PLA(2) inhibitors.
- Analysis of Lp-PLA(2) activity, plaque size, and necrotic core area.
Main Results:
- Selective Lp-PLA(2) inhibition reduces plasma Lp-PLA(2) activity.
- Inhibition also decreases atherosclerotic plaque area and necrotic core size.
- Lp-PLA(2) generates lysophosphatidylcholine and oxidized fatty acids, contributing to plaque instability.
Conclusions:
- Lp-PLA(2) plays a significant proatherogenic role.
- Selective inhibition of Lp-PLA(2) is a promising therapeutic approach for atherosclerosis.
- Further research into Lp-PLA(2) inhibitors is warranted.
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