Brewster Luke, Brey Eric M, Addis Michael, Xue Lian, Husak Vicki, Ellinger Joan, Haudenschild Christian C, Greisler Howard P
Department of Surgery, Loyola University, 2160 South First Avenue, Maywood, IL 60153, USA.
Am J Surg. 2006 Nov;192(5):589-93. doi: 10.1016/j.amjsurg.2006.08.005.
Chimeric proteins may be used to direct cell-specific activity. Heparin-binding growth-associated molecule (HBGAM) binds to cell receptors that are relatively more robust on endothelial cells, and it may confer endothelial cell selectivity to potent angiogens such as fibroblast growth factor-1 (FGF-1).
By ligating fibroblast growth factor or its potent mutant, S130K, to HBGAM, we tested their effect on re-endothelialization after angioplasty injury by using a canine model.
Both HBGAM/S130K- and HBGAM/FGF-1-treated arteries had increased neointimal mitotic index and re-endothelialization rates at 30 days compared with control arteries without inducing a significant increase in the neointimal thickness or the ratio of neointimal to medial thickness between treatment and control groups.
HBGAM/S130K and HBGAM/FGF-1 facilitates endothelial healing without myointimal thickening after canine carotid artery balloon angioplasty injury. Application of these growth factors in fibrin glue may improve endothelialization clinically after angioplasty or endarterectomy.
嵌合蛋白可用于指导细胞特异性活性。肝素结合生长相关分子(HBGAM)与内皮细胞上相对更稳定的细胞受体结合,并且它可能赋予强效血管生成素(如成纤维细胞生长因子-1,FGF-1)内皮细胞选择性。
通过将成纤维细胞生长因子或其强效突变体S130K与HBGAM连接,我们使用犬模型测试了它们对血管成形术损伤后再内皮化的影响。
与未诱导内膜厚度或治疗组与对照组之间内膜与中膜厚度比值显著增加的对照动脉相比,HBGAM/S130K和HBGAM/FGF-1处理的动脉在30天时内膜有丝分裂指数和再内皮化率均增加。
HBGAM/S130K和HBGAM/FGF-1可促进犬颈动脉球囊血管成形术损伤后内皮愈合而无肌内膜增厚。这些生长因子在纤维蛋白胶中的应用可能在临床上改善血管成形术或动脉内膜切除术后的内皮化。