Dattilo J B, Lust R M, Dattilo M P, Parker F M, Meadows W M, Sun Y S, Chitwood W R, Makhoul R G
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 27858, USA.
J Surg Res. 1997 May;69(2):349-53. doi: 10.1006/jsre.1997.5076.
The success of coronary reconstructive procedures is limited by the high incidence of restenosis secondary to intimal hyperplasia (IH). Transforming growth factor-beta 1 (TGF-beta 1) is a growth factor which has been shown to be important in the early development of IH in arteries and peripheral vein grafts. To date, there is little information concerning the early remodeling in aortocoronary vein grafts (ACVG). The purpose of this study was to characterize the expression of TGF-beta 1 expression in early aortocoronary vein grafts. Eighteen mongrel dogs underwent aortocoronary vein bypass grafting. Vein grafts were excised at 2 hr, 4 hr, and 7 days after implantation, snap frozen, and processed for ribonuclease protection assays (RPA) using 32P-labeled riboprobes for TGF-beta 1 and 18 S rRNA. TGF-beta 1 expression was quantified by densitometric analysis of autoradiographs which were expressed as a ratio TGF-beta 1/rRNA. Representative vessel rings were also collected for histology. There was a significant rise in TGF-beta 1 expression in the 2-hr vein grafts (0.42 +/- 0.04 compared to control saphenous vein (0.21 +/- 0.05, P < 0.02). In addition, there was significant downregulation of TGF-beta 1 at 4 hr (0.28 +/- 0.05) and at 7 days (0.18 +/- 0.01) when compared to 2 hr (P < 0.05). Histological specimens showed minimal intimal hyperplasia at 7 days. These results show for the first time an acute rise in TGF-beta 1 expression in ACVG. This upregulation quickly subsides by 4 hr and gene expression approaches control values by 7 days. By understanding this temporal relationship of expression one could better target potential therapeutic modalities to attenuate IH.
冠状动脉重建手术的成功率受到内膜增生（IH）继发再狭窄高发生率的限制。转化生长因子-β1（TGF-β1）是一种生长因子，已被证明在动脉和外周静脉移植物中IH的早期发展中起重要作用。迄今为止，关于主动脉冠状动脉静脉移植物（ACVG）早期重塑的信息很少。本研究的目的是表征TGF-β1在早期主动脉冠状动脉静脉移植物中的表达特征。18只杂种犬接受了主动脉冠状动脉静脉搭桥术。在植入后2小时、4小时和7天切除静脉移植物，速冻，并使用针对TGF-β1和18 S rRNA的32P标记核糖探针进行核糖核酸酶保护分析（RPA）。通过对放射自显影片的光密度分析对TGF-β1表达进行定量，其表示为TGF-β1/rRNA的比值。还收集代表性血管环用于组织学检查。2小时静脉移植物中TGF-β1表达显著升高（0.42±0.04，而对照大隐静脉为0.21±0.05，P<0.02）。此外，与2小时相比，4小时（0.28±0.05）和7天（0.18±0.01）时TGF-β1显著下调（P<0.05）。组织学标本在7天时显示内膜增生最小。这些结果首次表明ACVG中TGF-β1表达急性升高。这种上调在4小时时迅速消退，到7天时基因表达接近对照值。通过了解这种表达的时间关系，人们可以更好地靶向潜在的治疗方式以减轻内膜增生。
