Regulation of Vascular Genes by Glucose

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.

The involvement of phosphatidylinositol 3-kinase /Akt signaling in high glucose-induced downregulation of GLUT-1 expression in ARPE cells

“…The downregulation of GLUT1 expression in diabetic animals has been shown in the retina but not the cerebrum (Fernandes et al, 2004;Badr et al, 2000). Although chronic hyperglycemia is known to affect gene expression in a number of tissues and cells (Stenina, 2005), the alteration of GLUT-1 mRNA levels was not involved in the downregulation of GLUT-1 protein in the present study. These results are consistent with a study that reported that high glucose did not affect GLUT1 mRNA levels in bovine RPE cells (Fernandes et al, 2004).…”

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin–angiotensin system

“…In contrast, type 1 diabetic individuals (the remaining 5%) typically show no signs of metabolic syndrome and have low levels of insulin due to the destruction of pancreatic beta cells. Both, glucose and insulin have been implicated in gene regulation that may promote the development of cardiovascular disease in diabetic patients [1,2].…”

Cell Type-specific Post-transcriptional Regulation of Production of the Potent Antiangiogenic and Proatherogenic Protein Thrombospondin-1 by High Glucose

“…In vascular cells, glucose regulates expression of many genes that have been linked to the development of atherosclerosis or abnormal angiogenesis (reviewed in Ref. 7). One of them is thrombospondin-1 (TSP-1), 3 a cell matrix protein implicated in both atherogenesis (8 -12) and angiogenesis (13)(14)(15)(16)(17)(18)(19).…”