Abstract:
:Both the risk and the rate of development of atherosclerosis are increased in diabetics, but the mechanisms involved are unknown. Here we report a glucose-mediated increase in CD36 mRNA translation efficiency that results in increased expression of the macrophage scavenger receptor CD36. Expression of CD36 was increased in endarterectomy lesions from patients with a history of hyperglycemia. Macrophages that were differentiated from human peripheral blood monocytes in the presence of high glucose concentrations showed increased expression of cell-surface CD36 secondary to an increase in translational efficiency of CD36 mRNA. We obtained similar data from primary cells isolated from human vascular lesions, and we found that glucose sensitivity is a function of ribosomal reinitiation following translation of an upstream open reading frame (uORF). Increased translation of macrophage CD36 transcript under high glucose conditions provides a mechanism for accelerated atherosclerosis in diabetics.
journal_name
Nat Medjournal_title
Nature medicineauthors
Griffin E,Re A,Hamel N,Fu C,Bush H,McCaffrey T,Asch ASdoi
10.1038/89969keywords:
subject
Has Abstractpub_date
2001-07-01 00:00:00pages
840-6issue
7eissn
1078-8956issn
1546-170Xpii
89969journal_volume
7pub_type
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