© 2000 American Heart Association, Inc.
Vascular Biology |
Protein-Tyrosine Phosphatases in the Vessel Wall
Differential Expression After Acute Arterial Injury
From the Department of Pathology, University of Washington, Seattle. Dr Wright is now at the Department of Preclinical Cardiovascular Research, F. Hoffmann-La Roche, Basel, Switzerland.
Abstract—Many protein-tyrosine
phosphatases (PTPases) have now been identified, but little is known
about PTPase expression and regulation in vascular tissue and in
vascular disease. Polymerase chain reaction (PCR) amplification and
cDNA fingerprinting of PTPase catalytic domains, combined with random
sequencing of PCR product libraries, identified 18 (8 receptor-like
and 10 cytosolic) PTPases in the rat carotid artery and revealed
differential expression of 5 of these PTPases during
neointima formation after balloon catheter injury. In situ
hybridization was used to localize mRNA expression in vessel cross
sections for the 5 differentially expressed PTPases. This revealed that
for 3 PTPases (SHP1, CD45, and PTPß), differential transcript
abundance was due to appearance/loss of the cell types by which they
were expressed (leukocytes for SHP1 and CD45,
endothelial cells for PTPß). However, mRNA expression
of 2 PTPases (PTPL1 and PTP1B) was specifically upregulated by
proliferating and migrating smooth muscle cells (SMCs) in
characteristic temporal and regional patterns in response to vessel
damage. Quantitative PCR analysis showed that PTP1B and
PTPL1 were induced 
30-fold and 60-fold, respectively, by 2 weeks
after injury in the damaged vessels compared with the uninjured
vessels. PTP1B was rapidly upregulated in the media after vessel injury
and remained highly expressed in the developing neointima.
By contrast, PTPL1 expression did not increase dramatically until the
SMCs had migrated into the intima. The differential expression of PTP1B
and PTPL1 by SMCs after injury suggests roles for these PTPases in the
regulation of vessel wall remodeling.
Key Words: protein-tyrosine phosphatase • smooth muscle cells • injury • neointima • carotid arteries
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