on June 16, 2003
Published online before print June 16, 2003, doi: 10.1161/01.CIR.0000074223.56882.97
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Submitted on January 24, 2003
From the Joseph J. Jacobs Center for Thrombosis and Vascular Biology (O.I.S., I.K., E.J.T., E.F.P.), Department of Molecular Cardiology (O.I.S., I.K., E.J.T., E.F.P.), and Department of Cardiovascular Medicine (K.W., Z.Z., F.F., M.S.P., E.J.T.), Cleveland Clinic Foundation, Cleveland, Ohio. * To whom correspondence should be addressed. E-mail: plowe{at}ccf.org.
Background--Thrombospondin-1 (TSP-1) expression in the vascular wall has been related to the development of atherosclerotic lesions and restenosis. TSP-1 promotes the development of neointima and has recently been associated with atherogenesis at a genetic level. Because TSP-1 expression is responsive to glucose stimulation in mesangial cells, we hypothesized that glucose may stimulate its production by vascular cells. Thus, TSP-1 expression in the blood vessel wall may increase, providing a molecular link between diabetes and accelerated vascular lesion development. Methods and Results--To determine whether the expression level of TSP-1 in vessel wall is increased in diabetes, aorta and carotid arteries of Zucker rats were used for immunostaining, Western blotting, and in situ RNA hybridization. A significant increase in TSP-1 expression was found in the adventitia of blood vessels from diabetic rats. Consistent with the well-known antiangiogenic effect of TSP-1, the number of vasa vasorum was reduced in aortas from diabetic rats. In cultured endothelial cells, vascular smooth muscle cells, and fibroblasts, TSP-1 expression increased in response to glucose stimulation (>30-fold). After balloon catheter injury to carotid arteries, expression of TSP-1 protein and mRNA was higher at all time points in the vessels of diabetic rats. Conclusions--Increased expression of TSP-1 in blood vessels in diabetes may represent a new link between diabetes, atherogenesis, and accelerated restenosis. This increase in TSP-1 production may be a direct response of vascular cells to glucose.
Accepted on March 17, 2003
Increased Expression of Thrombospondin-1 in Vessel Wall of Diabetic Zucker Rat
Olga I. Stenina PhD,
Key words: diabetes mellitus • aorta • cardiovascular diseases • glucose
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