First published online October 10, 2007
Journal of Cell Science 120, 2001e (2007)
© The Company of Biologists Limited
Atherogenesis: cholesterol quashes TGF-
High levels of cholesterol are a major risk factor for atherosclerosis and, consequently, heart attacks and strokes. But how does cholesterol affect atherogenesis? Partly, report Jung San Huang and co-workers, by suppressing the responsiveness of vascular cells to the anti-atherosclerotic molecule transforming growth factor 
(TGF-; see p. 3509). TGF- antagonizes many key atherogenic events (for example, inflammation of blood vessel walls); so modulating responsiveness to TGF- is likely to affect the development of atherosclerosis. The authors show that cholesterol treatment suppresses TGF--induced signalling in several cell types, including endothelial cells. It does this, they report, by increasing the accumulation of TGF- receptors in lipid microdomains and facilitating the degradation of TGF-. By contrast, agents that lower or deplete cholesterol promote TGF--induced signalling. Finally, the authors show that TGF- responsiveness is suppressed in the aortic endothelium of atherosclerosis-prone mice fed a cholesterol-rich diet. These new insights into how cholesterol contributes to atherogenesis could lead to the development of new strategies for the treatment and prevention of atherosclerosis.
Related articles in JCS:
- Cholesterol suppresses cellular TGF- responsiveness: implications in atherogenesis
- Chun-Lin Chen, I-Hua Liu, Steven J. Fliesler, Xianlin Han, Shuan Shian Huang, and Jung San Huang
JCS 2007 120: 3509-3521.
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