Cholesterol trafficking, lysosomal function, and atherosclerosis.

Despite years of study and major research advances over the past 50 years, atherosclerotic diseases continue to rank as the leading global cause of death. Accumulation of cholesterol within the vascular wall remains the main problem and represents one of the early steps in the development of atherosclerotic lesions. There is a complex relationship between vesicular cholesterol transport and atherosclerosis, and abnormalities in cholesterol trafficking can contribute to the development and progression of the lesions.

ShcA promotes chondrocyte hypertrophic commitment and osteoarthritis in mice through RunX2 nuclear translocation and YAP1 inactivation.

Objective: Chondrocyte hypertrophic differentiation, a key process in endochondral ossification, is also a feature of osteoarthritis leading to cartilage destruction. Here we investigated the role of the adaptor protein Src homology and Collagen A (ShcA) in chondrocyte differentiation and osteoarthritis.

Methods: Mice ablated for ShcA in osteochondroprogenitor cells were generated by crossing mice carrying the Twist2-Cre transgene with ShcA mice.

Wnt5a Promotes Lysosomal Cholesterol Egress and Protects Against Atherosclerosis.

Background: Impairment of cellular cholesterol trafficking is at the heart of atherosclerotic lesions formation. This involves egress of cholesterol from the lysosomes and 2 lysosomal proteins, the NPC1 (Niemann-Pick C1) and NPC2 that promotes cholesterol trafficking. However, movement of cholesterol out the lysosome and how disrupted cholesterol trafficking leads to atherosclerosis is unclear.

atherosclerosis: gone with the Wnt?

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.

Author Correction: Loss of the adaptor protein ShcA in endothelial cells protects against monocyte macrophage adhesion, LDL-oxydation, and atherosclerotic lesion formation.

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