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Platelet-derived Growth Factor And Its Receptor In The Regulation Of Hypoxic Pulmonary Vascular Smooth Muscle Cell Proliferation And Its Molecular Mechanism

Posted on:2000-11-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q H HuangFull Text:PDF
GTID:1114360185469477Subject:Pathophysiology
Abstract/Summary:PDF Full Text Request
Pulmonary hypertension can be caused by exposing animals to chronic hypoxia. Hypoxia causes proliferation and hypertrophy of SMCs in pulmonary arterial wall and accumulation of extracellular matrix components as well as muscularization of nonmuscular intra-acinar vessels and medial smooth muscle cell. These structural changes are characteristics of pulmonary vascular remodeling that lead to hypoxic pulmonary hypertension. Growth factors including Platelet-derived growth factor(PDGF) operate the lung vascular remodeling in hypoxia are not clear.PDGF is a potent mitogen for cells of mesenchymal origin, a stimulator for connective tissue-forming cells to produce extracellular matrices and a potent vasoconstrictor. PDGF is not only produced by platelets but also by vascular endothelial cells, macrophages, fibroblasts and smooth muscle cells under certain conditions. Nevertheless, little is known about the role of PDGF in the hypoxic pulmonary hypertension. Here we made a systematical study on the mechanism of hypoxic pulmonary vascular medial hyperplasia involved in PDGF and its receptor. Heparin is widely regarded as a cell growth antagonist, its precise manner is still unknown. This study is designed to investigate the inhibition of mitogenesis by heparin in hypoxic rats and cultured bovine pulmonary artery smooth muscle cells(PASMCs) and to identify major signal transduction pathways involved.1. The study on the probable mechanisms of hypoxia-induced PDGF/itsreceptor gene expression and PASMCs proliferation (1) The effect of hypoxia (5%CO295%N2) on PDGF-A,B chains and α,βreceptors gene expression both in vivo and in vitro. These four kinds ofgene expression were assessed by in situ hybridization.Pulmonary hypertension remodeling in rats and hypoxic PASMC remodeling in cultured neonatal bovine pulmonary vascular smooth muscle cells were constructed. We prepared specific PDGF-A ,B chain and PDGF- α, β receptor cDNA probes. In situ hybridization analysis revealed that PDGF-A chain mRNA level in the lungs was increased, reached a maximum of day...
Keywords/Search Tags:Platelet-derived
PDF Full Text Request
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