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Cardiovascular Research 1996 31(1):28-36; doi:10.1016/S0008-6363(95)00144-1
© 1996 by European Society of Cardiology
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Copyright © 1996, European Society of Cardiology

Expression of transforming growth factor-β1 (TGF-β1) and urokinase-type plasminogen activator (u-PA) genes during arterial repair in the pig

Stanislaw J. Wysocki*,a, Ming-Hao Zhengb, Ying Fanc, M.D. Lamawansad,1, Anthony K. Housed and Paul E. Normana

aDepartment of Surgery, University of Western Australia, Fremantle Hospital, PO Box 480, Fremantle, W.A. 6160, Australia
bDepartment of Orthopaedic Surgery, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, W.A., Australia
cDepartment of Pathology, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, W.A., Australia
dDepartment of Surgery, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, W.A., Australia

* Corresponding author.

Objective: The transition from quiescence to proliferation in vitro is accompanied by early expression of proliferation-associated genes encoding products including cytokines and enzymes. We aimed to investigate TGF-β1, u-PA and PAI-1 gene expressions in relation to proliferation and extracellular matrix (ECM) protein gene expressions in porcine arteries following injury. Methods: Right iliac arteries of juvenile pigs were de-endothelialised and harvested at fixed times after injury. RNA was then extracted and analysed by Northern blot analysis. RNA transcripts in thickened neointima of arteries were examined by in situ hybridisation using digoxygenin-labelled cDNA probes. Results: TGF-β1, u-PA and PAI-1 transcripts were rapidly elevated (2–8h) and preceded a peak in histone mRNA at 24h after arterial injury. A second prolonged rise in TGF-β1 mRNA at 4d coincided with elevated ECM protein gene expressions. TGF-β1 gene expression was detected in neointimal cells lining the arterial lumen at 4wk after injury. Conclusions: The timings of increases in TGF-β1, u-PA and PAI-1 mRNAs in injured arteries are consistent with contributions to processes prior to proliferation. The observation of a second protracted elevation in TGF-β1 expression is supportive of an additional role in stimulation of ECM protein synthesis. Functional specialisation exists within the thickened intima of arteries late in repair.

KEYWORDS Gene expression; Restenosis; Transforming growth factor-β1; Urokinase-type plasminogen activator; Plasminogen activator inhibitor-1; Pig arteries

1 Current address: Department of Surgery, University of Peradeniya, Peradeniya, Sri Lanka.


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