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Updated: Feb 12, 2026
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Can modulators of apolipoproteinB biogenesis serve as an alternate target for cholesterol-lowering drugs?
Lynley M Doonan1, Edward A Fisher2, Jeffrey L Brodsky1
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, United States.
Abstract:
Understanding the molecular defects underlying cardiovascular disease is necessary for the development of therapeutics. The most common method to lower circulating lipids, which reduces the incidence of cardiovascular disease, is statins, but other drugs are now entering the clinic, some of which have been approved. Nevertheless, patients cannot tolerate some of these therapeutics, the drugs are costly, and/or the treatments are approved for only rare forms of disease. Efforts to find alternative treatments have focused on other factors, such as apolipoproteinB (apoB), which transports cholesterol in the blood stream. The levels of apoB are regulated by endoplasmic reticulum (ER) associated degradation as well as by a post ER degradation pathway in model systems, and we suggest that these events provide novel therapeutic targets. We discuss first how cardiovascular disease arises and how cholesterol is regulated, and then summarize the mechanisms of action of existing treatments for cardiovascular disease. We then review the apoB biosynthetic pathway, focusing on steps that might be amenable to therapeutic interventions.
Insights
New cardiovascular disease therapeutics targeting apolipoproteinB (apoB) degradation offer alternatives to statins. Understanding apoB regulation provides novel therapeutic targets for managing cholesterol levels and reducing cardiovascular disease risk.
Area of Science:
- Cardiovascular Science
- Molecular Biology
- Pharmacology
Background:
- Cardiovascular disease (CVD) necessitates novel therapeutics beyond statins due to patient intolerance, cost, and limited application.
- ApolipoproteinB (apoB) is a key cholesterol transporter, making its regulation a potential therapeutic target.
- Existing lipid-lowering drugs have limitations, driving research into alternative treatment strategies.
Purpose of the Study:
- To explore apolipoproteinB (apoB) as a therapeutic target for cardiovascular disease.
- To review existing cardiovascular disease treatments and their limitations.
- To investigate apoB regulation pathways for potential therapeutic interventions.
Main Methods:
- Review of existing literature on cardiovascular disease, cholesterol regulation, and current therapeutics.
- Analysis of the apolipoproteinB (apoB) biosynthetic pathway.
- Discussion of endoplasmic reticulum (ER)-associated degradation and post-ER degradation pathways of apoB.
Main Results:
- Statins are common but not universally effective or tolerated.
- ApolipoproteinB (apoB) levels are regulated by ER-associated and post-ER degradation.
- Specific steps in the apoB pathway present potential therapeutic intervention points.
Conclusions:
- Targeting apoB degradation pathways offers a promising alternative for cardiovascular disease treatment.
- Understanding molecular defects in apoB regulation can lead to novel therapeutic strategies.
- Further research into apoB modulation could improve cardiovascular disease management.
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