The Role Of Tumor Necrosis Factor ¦Á, Vascular Endothelial Cell Pdgf-b Chain Gene Transcription Regulation Research

Atherosclerosis (AS) is a principal cause of many lethal diseases. However, its mechanisms have not been fully educidated. It has increasingly been regarded that AS is a chronic inflammatory process, in which the central event is the dysfunction of arterial wall endothelial cells (EC) and the later proliferation of smooth muscle cells. A few related pathogenic factors somehow lead to endothelial dysfunction, which can elicit a series of cellular interactions that culminate in the lesions of AS. Tumor necrosis factor α(TNF α ), which is a cytokine with multiple bioactive effect, is present in human typical atherosclerotic lesions with the positive rate as high as 90%. Interestingly, platelet-derived growth factor (PDGF), which is a dimer (PDGF-AA, PDGF-BB and PDGF-AB), increases obviously in the lesions of AS. It has been reported that TNF α could stmulate the expression of endothelial PDGF-B mRNA, which is encoded by PDGF-B chain gene.However, the molecular mechanisms controlling PDGF-B chain gene transcription are few known now. The ways through which TNF α stimulates the transcription of PDGF-B chain gene in vascular EC are not reported yet. The goal of this study is gain insight into the regulation of PDGF-B chain gene expression in EC treated with TNF α , which would be important to clarify the mechanisms of AS. For this poupose, the following aspects are studied: 1) The effect of TNF α on PDGF-B mRNA level in vascular EC; 2) The regulatory effect of upstream sequence on TNF α -induced PDGF-B chain gene transcription in vascular EC; 3) The role of calcium ion (Ca²⁺) in upstream sequence...