Protein-tyrosine phosphatases in the vessel wall - Differential expressionafter acute arterial injury

Many protein-tyrosine phosphatases (PTPases) have now been identified, but little is known about PTPase expression and regulation in vascular tissue a nd in vascular disease. Polymerase chain reaction (PCR) amplification and c DNA fingerprinting of PTPase catalytic domains, combined with random sequen cing of PCR product libraries, identified 18 (8 receptor-like and 10 cytoso lic) PTPases in the rat carotid artery and revealed differential expression of 5 of these PTPases during neointima formation after balloon catheter in jury. In situ hybridization was used to localize mRNA expression in vessel cross sections for the 5 differentially expressed PTPases. This revealed th at for 3 PTPases (SHP1, CD45, and PTP beta), differential transcript abunda nce was due to appearance/loss of the cell types by which they were express ed (leukocytes for SHP1 and CD45, endothelial cells for PTP beta), However, mRNA expression of 2 PTPases (PTPL1 and PTP1B) was specifically upregulate d by proliferating and migrating smooth muscle cells (SMCs) in characterist ic temporal and regional patterns in response to vessel damage. Quantitativ e PCR analysis showed that PTP1B and PTPL1 were induced approximate to 30-f old and approximate to 60-fold, respectively, by 2 weeks after injury in th e damaged vessels compared with the uninjured vessels. PTP1B was rapidly up regulated in the media after vessel injury and remained highly expressed in the developing neointima. By contrast, PTPL1 expression did not increase d ramatically until the SMCs had migrated into the intima. The differential e xpression of PTP1B and PTPL1 by SMCs after injury suggests roles for these PTPases in the regulation of vessel wall remodeling.