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Involvement of transforming growth factor-beta in regulation of calcium transients in diabetic vascular smooth muscle cells.

Authors: Sharma, K  Deelman, L  Madesh, M  Kurz, B  Ciccone, E  Siva, S  Hu, T  Zhu, Y  Wang, L  Henning, R  Ma, X  Hajnoczky, G 
Citation: Sharma K, etal., Am J Physiol Renal Physiol 2003 Dec;285(6):F1258-70.
Pubmed: (View Article at PubMed) PMID:12876066
DOI: Full-text: DOI:10.1152/ajprenal.00145.2003

Altered calcium [Ca2+] transients of vascular smooth muscle cells to vasoconstrictors may contribute to altered regulation of blood flow in diabetes. We postulated that diabetes-induced transforming growth factor (TGF)-beta production contributes to impaired ANG II response of vascular smooth muscle cells in macrovessels and microvessels. Aortic vascular smooth muscle cells isolated from diabetic rats exhibited markedly impaired ANG II-induced cytosolic calcium [Ca2+] signal that was completely restored by pretreatment with anti-TGF-beta antibodies. Similar findings were noted in microvascular smooth muscle cells isolated from preglomerular vessels and cultured in high glucose. The impact of diabetes on [Ca2+] transients was replicated by addition of TGF-beta1 and -beta2 isoforms to aortic smooth muscle cells in culture and diabetic cells had enhanced production of TGF-beta2. In the in vivo condition, TGF-beta1 was increased in diabetic glomeruli, whereas TGF-beta2 was increased in diabetic aorta. The characteristic increase in glomerular filtration surface area found in diabetic rats was prevented by treatment with anti-TGF-beta antibodies, and impaired ANG II-induced aortic ring contraction in diabetic rats was completely restored by anti-TGF-beta antibodies. Impaired vascular dysfunction may be partly due to decreased inositol 1,4,5-trisphosphate receptor (IP3R), as reduced type I IP3R expression was found in diabetic aorta and restored by anti-TGF-beta antibodies. We conclude that TGF-beta plays an important role in the vascular dysfunction of early diabetes by inhibiting calcium transients in vascular smooth muscle cells.

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CRRD Object Information
CRRD ID: 731229
Created: 2003-12-30
Species: All species
Last Modified: 2004-08-23
Status: ACTIVE



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