angiogenesis blood vessel growth :: essays research papers

PDFG induces proliferation of fibroblasts, microglia, and smooth muscle. It is stored in platelet granules and is released following platelet aggregation. PDGF may also serve as a chemotactic agent for inflammatory cells. Platelets circulate in the blood and are derived from megakaryocytic in the marrow. Like erythrocytes, they are anucleate. However, unlike erythrocytes, they contain numerous intracytoplasmic granules and are the source of numerous proinflammatory mediators. In fact, they are quantitatively the greatest single source of vasoactive amines in the body. They also are a rich source of thromboxane A2. It is their activation that, in part, initiates the vascular phase of the acute inflammatory response (see Fig. 2-13 in text). To have them play this role makes imminently good sense, because they are present in large numbers throughout the circulation, i.e., some are always in close proximity to an inciting stimulus. Vasoactive Literally translated, this adjective means that a substance has the capacity to alter the physiologic state, especially the tone and caliber, of a vessel. Platelet-Derived Growth Factor (PDGF), a dimeric glycoprotein composed of two A and/or B chains, is the principal mitogen in serum for mesenchymal cells. Applications include culture of various cell types derived from connective tissue. It can also be used to study chemotaxis, wound healing, and bone repair. Another member of the PDGF family is the Vascular Endothelial Growth Factor (VEGF) with endothelial cell-specific activities (e.g., angiogenic and mitogenic factor). Platelet-derived growth factor (PDGF) [1-3 reviews], a factor released from platelets upon clotting, is responsible for stimulating the proliferation of fibroblasts in vitro [4-6]. PDGF is also produced by a number of cell types besides platelets and is mitogen for vascular smooth muscle cells, bone cells, cartilage cells, connective tissue cells and some blood cells [7-9]. PDGF is stored in platelet alpha granules and released upon platelet activation. PDGFs are disulfide-linked dimers. The subunits of the PDGF dimers are homologous polypeptides designated PDGF-A and PDGF-B chains. Natural PDGFs can exist either as homodimers (PDGF-AA, PDGF-BB) or heterodimers (PDGF-AB). Two splice variants exist for the A-chain (211AA for the long isoform, 196AA for the most abundant short isoform), and C-terminal proteolytic processing apparently occurs for the B-chain (and possibly the A-chain) [10-12]. A-chain long isoform and B-chain contain a cell retention signal at the C-term end, which must be removed in order to release a freely circulating PDGF [13-16]. Two distinct human PDGF receptor transmembrane binding proteins have been identified [17,18].