In a porcine model of arterial injury, early increases in TGF-beta1, u-PA, and PAI-1 mRNAs precede cellular proliferation, while a later prolonged elevation in TGF-beta1 supports its role in stimulating extracellular matrix protein synthesis during arterial repair.
Supports sequential TGF-beta1 roles in arterial repair; leaves open translation to human restenosis therapies.
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-beta1, 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-beta1, 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-beta1 mRNA at 4d coincided with elevated ECM protein gene expression. TGF-beta1 gene expression was detected in neointimal cells lining the arterial lumen at 4wk after injury. CONCLUSIONS: The timings of increases in TGF-beta1, 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-beta1 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.
No takes yet. Share an insight, caveat, or question.
Wysocki et al. (1996) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: