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Updated: Dec 24, 2025
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
atherosclerosis: gone with the Wnt?
Philippe Boucher1, Rachel L Matz1, Jérôme Terrand1
1CNRS, UMR 7021, University of Strasbourg, 67401, Illkirch, France.
Insights
Wnt signaling influences cellular cholesterol accumulation, a key factor in atherosclerosis. Understanding this pathway offers new therapeutic strategies for cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Cellular Metabolism
- Molecular Signaling
Background:
- Atherosclerosis is a leading cause of cardiovascular disease, characterized by cholesterol accumulation in arterial cells.
- Foam cell formation, driven by modified low-density lipoprotein uptake, is central to atherosclerotic lesion development.
- Recent research has illuminated early lesion formation, cholesterol transport, and vascular inflammation.
Purpose of the Study:
- To review the role of Wnt signaling in regulating cellular cholesterol accumulation.
- To explore Wnt signaling's impact on pathways limiting cholesterol buildup.
- To highlight Wnt signaling's potential in atherosclerotic disease development and progression.
Main Methods:
- Literature review focusing on Wnt signaling and cholesterol metabolism.
- Analysis of Wnt signaling's effects on lysosomal function and related pathways.
- Examination of Wnt signaling's influence in arterial wall cells (smooth muscle cells, endothelial cells, macrophages).
Main Results:
- Wnt signaling affects lysosomal function, a key regulator of cellular cholesterol levels.
- This signaling pathway impacts pathways that limit cholesterol accumulation in various cell types.
- Wnt signaling plays a significant role in the development and progression of atherosclerosis.
Conclusions:
- Wnt signaling is an underappreciated factor in atherosclerosis pathogenesis.
- Targeting Wnt signaling pathways may offer novel therapeutic avenues for cardiovascular disease.
- Further research into Wnt signaling's role in cholesterol homeostasis is warranted.
Abstract:
Atherosclerosis, a pathology affecting large and medium-sized arteries, is the major cause of cardiovascular morbidity/mortality in industrialized countries. During atherosclerosis, cells accumulate large amounts of cholesterol through the uptake of modified low-density lipoprotein particles to form foam cells. This accumulation forms the basis for the development of the disease and for a large spectrum of other diseases in various organs. Massive research efforts have yielded valuable information about the underlying molecular mechanisms of atherosclerosis. In particular, newer discoveries on the early stage of lesion formation, cholesterol accumulation, reverse cholesterol transport, and local inflammation in the vascular wall have opened unanticipated horizons of understanding and raised novel questions and therapeutic opportunities. In this review, we focus on Wnt signaling, which has received little attention so far, yet affects lysosomal function and signalling pathways that limit cholesterol accumulation. This occurs in different tissues and cell types, including smooth muscle cells, endothelial cells and macrophages in the arterial wall, and thus profoundly impacts on atherosclerotic disease development and progression.
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