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The Protein NPC1 Polices Macrophage Cholesterol Traffic

Date:
May 16, 2008
Source:
Journal of Clinical Investigation
Summary:
Atherosclerosis is a disease of the arterial blood vessels that is often known as hardening of the arteries. It is caused in part by the accumulation in the artery wall of cells (mostly cells known as macrophages) that contain fats (mostly cholesterol).
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Atherosclerosis is a disease of the arterial blood vessels that is often known as hardening of the arteries. It is caused in part by the accumulation in the artery wall of cells (mostly cells known as macrophages) that contain fats (mostly cholesterol).

Understanding how macrophages regulate the amount and type of cholesterol they contain is therefore of importance for understanding the mechanisms underlying atherosclerosis. Daniel Ory and colleagues, at the University of Washington School of Medicine, St. Louis, have now provided new insight into this, showing that the protein NPC1 is a factor protecting mice from atherosclerosis through its function as a regulator of macrophage cholesterol trafficking.

Mice lacking LDLR develop atherosclerosis when fed a high-fat diet, but when the authors manipulated these mice such that their macrophages lacked both LDLR and NPC1 they developed atherosclerosis more rapidly. The accelerated atherosclerosis in the absence of NPC1 was associated with impaired cholesterol efflux from macrophages.

Further analysis revealed that NPC1 was required for the generation of 27-hydroxycholsterol, which binds proteins known as LXRs, and for the LXR-dependent upregulation of proteins involved in cholesterol efflux. These data suggest that variation in NPC1 gene expression might affect how susceptible an individual is to developing atherosclerosis.


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The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking. Journal of Clinical Investigation. May 15, 2008.

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Journal of Clinical Investigation. "The Protein NPC1 Polices Macrophage Cholesterol Traffic." ScienceDaily. ScienceDaily, 16 May 2008. <www.sciencedaily.com/releases/2008/05/080516163132.htm>.
Journal of Clinical Investigation. (2008, May 16). The Protein NPC1 Polices Macrophage Cholesterol Traffic. ScienceDaily. Retrieved July 5, 2015 from www.sciencedaily.com/releases/2008/05/080516163132.htm
Journal of Clinical Investigation. "The Protein NPC1 Polices Macrophage Cholesterol Traffic." ScienceDaily. www.sciencedaily.com/releases/2008/05/080516163132.htm (accessed July 5, 2015).

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