Jr. Hoch et al., THE TEMPORAL RELATIONSHIP BETWEEN THE DEVELOPMENT OF VEIN GRAFT INTIMAL HYPERPLASIA AND GROWTH-FACTOR GENE-EXPRESSION, Journal of vascular surgery, 22(1), 1995, pp. 51-58
Purpose: Intimal hyperplasia is a common cause of obstructive stenosis
after arterial reconstructive procedures. It has been postulated that
growth factors elaborated by vascular wall cells regulate fibroprolif
erative changes that can cause graft failure. This study characterizes
transforming growth factor beta-1 (TGP-beta 1) and platelet-derived g
rowth factor-ii chain (PDGF-A) mRNA transcript profiles and their temp
oral relationship to the development of intimal hyperplasia in vein gr
afts. Methods: Epigastric vein-to-common femoral artery interposition
grafts were performed in male Lewis rats (350 to 450 gm) with standard
microsurgical techniques. Grafts were harvested at 1 and 4 hours, 1 a
nd 4 days, and 1 and 2 weeks (n = 5/time). Graft RNA was extracted, re
verse-transcribed, and amplified by polymerase chain reaction with sen
se/antisense primers for TGF-beta 1 and PDGP-A (30 cycles). Polymerase
chain reaction fragments were confirmed by Southern hybridization. Re
sults: Variable induction of TGP-beta 1 gene transcription was evident
in vein grafts at 1 and 4 hours, with prominent mRNA expression from
1 day to 2 weeks. PDGF-A mRNA was detected in ungrafted control veins
but was downregulated at 1 hour and absent at 4 hours after grafting.
PDGF-A transcription was upregulated by 1 day, with prominent expressi
on from 4 days to 1 week. Early loss of PDGF-A mRNA correlated with th
e early denudation of the endothelium, whereas upregulation by 4 days
was preceded by TGF-beta 1 mRNA expression. Conclusions: Upregulation
of TGF-beta 1 and PDGF-A mRNA expression is detected in vein grafts be
fore the development of a quantifiable neointima, which occurs by 2 we
eks in our model. This suggests a role for these growth factors in the
development of vein graft intimal hyperplasia.