TGFbeta is active, and correlates with activators of TGFbeta, following porcine coronary angioplasty.
OBJECTIVE
Restenosis following angioplasty involves processes that may be influenced by local production of cytokines. We investigated the expression of active and total transforming growth factor beta (TGFbeta) following porcine coronary angioplasty (PTCA), and have correlated this with the expression of potential in vivo activators of TGFbeta: mannose-6-phosphate/insulin-like growth factor-II (M6P/IGF-II) receptor and thrombospondin-1.


METHODS
Oversized porcine PTCA was performed and the arteries excised after selected intervals. Levels of in situ active and total (active plus latent) TGFbeta were determined using a modified plasminogen activator-inhibitor/luciferase bioassay.


RESULTS
Levels of active TGFbeta significantly increased 2 h to 7 days after angioplasty, compared to non-injured controls. Levels returned to baseline by 28 days. Active TGFbeta in tissues adjacent to the injured artery did not change. Total TGFbeta was significantly higher than controls 2-6 h after injury. M6P/IGF-II receptor mRNA was upregulated between 6 h and 3 days after injury, with protein detectable at 3-28 days. Thrombospondin-1 was detected between 1 h and 14 days.


CONCLUSIONS
We conclude that balloon injury causes an early rapid increase in levels of active TGFbeta, that correlates with the expression of TGFbeta activators. Thus, TGFbeta is a good potential target for anti-restenotic therapies.
Cardiovascular Research Group, Section of Medicine, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK. j.chamberlain@sheffield.ac.uk
J
J
Chamberlain
J
J
Gunn
S E
SE
Francis
C M
CM
Holt
N D
ND
Arnold
D C
DC
Cumberland
M W
MW
Ferguson
D C
DC
Crossman
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D015153:Blotting, Western; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D012008:Recurrence; D013552:Swine; D019700:Thrombospondin 1 / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D017527:Receptor, IGF Type 2; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta