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Circadian Angiopoietin-Like-4 as a Novel Therapy in Cardiovascular Disease
Sydney Shuff1, Yoshimasa Oyama2, Lori Walker3
1Department of Anesthesiology, University of Colorado Denver School of Medicine, Aurora, CO, USA.
Abstract:
Angiopoietin-like 4 (ANGPTL4) is critical for regulating plasma lipids, and thus an attractive therapeutic target for cardiovascular diseases. Unfortunately, targeting ANGPTL4 results in a proinflammatory and ultimately lethal phenotype in animals. The serendipitous discovery of cardiac ANGPTL4 as a circadian protein reveals novel mechanistic insight and a solution for this therapeutic dilemma.
Insights
Angiopoietin-like 4 (ANGPTL4) regulates lipids but causes lethal inflammation. Discovering cardiac ANGPTL4 as a circadian protein offers a new therapeutic strategy for cardiovascular diseases.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Chronobiology
Background:
- Angiopoietin-like 4 (ANGPTL4) is a key regulator of plasma lipids.
- ANGPTL4 is a potential therapeutic target for cardiovascular diseases.
- Directly targeting ANGPTL4 leads to lethal inflammation in preclinical models.
Purpose of the Study:
- To investigate the role of cardiac ANGPTL4 in lipid metabolism.
- To explore the potential of ANGPTL4 as a therapeutic target for cardiovascular diseases.
- To address the safety concerns associated with ANGPTL4 inhibition.
Main Methods:
- Investigated ANGPTL4 expression and function in cardiac tissues.
- Utilized proteomic and genetic approaches to study ANGPTL4.
- Assessed the impact of ANGPTL4 modulation on lipid profiles and inflammatory markers.
Main Results:
- Cardiac ANGPTL4 exhibits circadian expression patterns.
- Circadian regulation of ANGPTL4 influences plasma lipid levels.
- This circadian property may mitigate the adverse inflammatory effects of ANGPTL4 targeting.
Conclusions:
- Cardiac ANGPTL4 is a circadian-regulated protein.
- Exploiting the circadian nature of ANGPTL4 presents a novel therapeutic avenue.
- This finding offers a potential solution to the ANGPTL4-associated inflammation dilemma in cardiovascular disease therapy.
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