Tyrosine kinase inhibition prevents deformation-stimulated vascular smooth muscle growth.
The goal of this study was to determine the role of tyrosine phosphorylation in transducing deformation-stimulated vascular smooth muscle growth. Rat aorta-derived vascular smooth muscle cells were cultured on flexible silicone elastomer membranes and subjected to cyclic deformation (15 cycles per minute, deformed 2 seconds, relaxed 2 seconds). Deformation significantly increased proto-oncogene expression, [3H]thymidine incorporation, [3H]leucine incorporation, and cell number. Time course studies showed an 8-hour lag between initiation of cell deformation and onset of [3H]thymidine incorporation, with peak levels achieved after 18 to 24 hours. Western analysis of protein blots from deformed cells (10 minutes) demonstrated increased levels of phosphotyrosine-containing proteins having molecular weights of 110 to 130 and 70 to 80 kD. Deformation-stimulated tyrosine phosphorylation was prevented by the tyrosine kinase inhibitor Herbimycin A. Tyrosine kinase inhibition also prevented deformation-stimulated vascular smooth muscle cell growth as measured by [3H]thymidine incorporation. Cyclic deformation stimulates vascular smooth muscle proliferation through activation of tyrosine kinases. Inhibition of tyrosine phosphorylation is an effective means of preventing deformation-induced vascular smooth muscle growth in vitro.
Davis
M G
MG
Department of Medicine/Cardiology, University of Cincinnati, Ohio 45267.
Ali
S
S
Leikauf
G D
GD
Dorn
G W
GW
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D010812:Physical Stimulation; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011519:Proto-Oncogenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D004247:DNA; D011505:Protein-Tyrosine Kinases