Author: Stenina, O. I.

Source: Current Pharmaceutical Design, Volume 11, Number 18, July 2005 , pp. 2367-2381(15)

Publisher: Bentham Science Publishers

Abstract:

Endothelial dysfunction is an early sign of diabetic vascular disease. Due to their unique position at the border between blood and vascular tissue, endothelial cells (EC) are the first vascular cells to sensor humoral changes, and they are able to transmit the information about these changes to other vascular cell types by changing their gene expression profile and producing growth factors, cytokines, adhesion molecules, and other bioactive molecules. These signals alter vascular cell dynamics and interactions, vascular tone and result in inability of the vessel to maintain athrombogenic luminal surface and in alteration of vascular permeability. Although researchers have yet to uncover the precise mechanism(s) that leads to diabetic vascular disease, hyperglycemia has been identified as an independent risk factor for micro- and macrovascular complications. Elevated levels of glucose induce the expression of a variety of genes related to atherogenesis and angiogenesis regulation. However, most of our current knowledge about the molecular mechanisms used by glucose to regulate gene expression is based on studies that used cells with insulin-dependent glucose transport (hepatocytes, adipocytes). Such cells are significantly different than vascular cells, in which glucose uptake is mostly imparted by insulin-independent mechanisms. This review summarizes current information about the effects of hyperglycemia and elevated glucose in in vitro systems on vascular gene expression and molecular transcriptional and post-transcriptional mechanisms that may regulate the changes related to diabetic vascular complications.

Keywords: atherosclerosis; angiogenesis; diabetes; endothelial cell; smooth muscle cell; transcription

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612054367283

Affiliations: 1: NB50, Department of Molecular Cardiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Publication date: 2005-07-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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