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New molecular targets for cholesterol-lowering therapy
N N Izzat1, M E Deshazer, D S Loose-Mitchell
1Department of Integrative Biology and Pharmacology, University of Texas Health Sciences Center, Houston, Texas 77225, USA.
The Journal of Pharmacology and Experimental Therapeutics
|April 25, 2000
Summary
Cholesterol-lowering statins significantly reduce cardiovascular and total mortality risk. New therapies targeting bile acid transport and cholesterol absorption offer additional strategies for managing cholesterol levels.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- Randomized clinical trials confirm that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce cardiovascular and total mortality.
- Risk reduction is observed across diverse patient populations, including those with and without pre-existing cardiovascular disease or varying plasma cholesterol levels.
Purpose of the Study:
- To review the established benefits of cholesterol-lowering therapies.
- To identify and discuss novel molecular targets for future cholesterol-lowering drug development.
Main Methods:
- Review of randomized clinical trials on statin efficacy.
- Identification and description of emerging therapeutic targets, including the Na(+)-dependent bile acid transporter, cholesterol absorption pathways, and transcriptional regulation of cholesterol 7alpha-hydroxylase.
Main Results:
- Statins effectively lower plasma cholesterol, slow atherosclerosis progression, and reduce ischemic events, potentially to levels below 100 mg/dl.
- Novel targets offer alternative mechanisms for cholesterol reduction beyond statin pathways.
Conclusions:
- Cholesterol-lowering treatment is a proven strategy for reducing mortality.
- Emerging targets like the bile acid transporter and cholesterol absorption mechanisms present promising avenues for new therapeutic interventions.