THE TEMPORAL RELATIONSHIP BETWEEN THE DEVELOPMENT OF VEIN GRAFT INTIMAL HYPERPLASIA AND GROWTH-FACTOR GENE-EXPRESSION

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 fibroproliferative changes that can cause graft failure. This study characterizes transforming growth factor beta-1 (TGP-beta 1) and platelet-derived growth factor-ii chain (PDGF-A) mRNA transcript profiles and their temporal relationship to the development of intimal hyperplasia in vein grafts. 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 and 4 days, and 1 and 2 weeks (n = 5/time). Graft RNA was extracted, reverse-transcribed, and amplified by polymerase chain reaction with sense/antisense primers for TGF-beta 1 and PDGP-A (30 cycles). Polymerase chain reaction fragments were confirmed by Southern hybridization. Results: 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 expression from 4 days to 1 week. Early loss of PDGF-A mRNA correlated with the 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 before the development of a quantifiable neointima, which occurs by 2 weeks in our model. This suggests a role for these growth factors in the development of vein graft intimal hyperplasia.