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A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation

Nature Medicine volume 7, pages 840–846 (2001)Cite this article

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.

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Figure 1: CD36 expression by tissue macrophages in vascular lesions.
Figure 2: Immunologic and functional expression of CD36.
Figure 3: RNA analysis.
Figure 4: Secondary structure of CD36 5′-UTR.
Figure 5: Role of CD36 5′-UTR in glucose-mediated increase in translation.
Figure 6: Mechanism of glucose-mediated increase in translation.

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Acknowledgements

We thank J. Han for the gift of labeled Ox-LDL; F. Pearce for advice on the Ox-LDL studies; A. Cerutti for help with some of the flow cytometry; and M.J.R. Echevarria, D. Falcone and R. Nachman for their critical review of the manuscript. This research was supported by grants from the NIH (DK48698) and American Heart Association (to A.S.A.) and from Universita degli Studi di Parma, Parma, Italy (to A.R.).

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  1. Weill Medical College of Cornell University, New York, New York, USA

    Erik Griffin, Alessandro Re, Nance Hamel, Chenzong Fu, Harry Bush, Timothy McCaffrey & Adam S. Asch

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Correspondence to Adam S. Asch.

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Griffin, E., Re, A., Hamel, N. et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med 7, 840–846 (2001). https://doi.org/10.1038/89969

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