A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation.
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.
Griffin
E
E
Weill Medical College of Cornell University, New York, NY, USA.
Re
A
A
Hamel
N
N
Fu
C
C
Bush
H
H
McCaffrey
T
T
Asch
A S
AS
D020121:5' Untranslated Regions; D001161:Arteriosclerosis / Q000150:complications*; D001483:Base Sequence; D018955:CD36 Antigens / Q000235:genetics*; D017931:DNA Primers; D048909:Diabetes Complications; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics
D020121:5' Untranslated Regions; D018955:CD36 Antigens; D017931:DNA Primers; D012333:RNA, Messenger; D005947:Glucose