Impaired endothelial cell proliferative, migratory, and adhesive abilities are associated with the slow endothelialization of polycaprolactone vascular grafts implanted into a hypercholesterolemia rat model
Impaired endothelial cell proliferative, migratory, and adhesive abilities are associated with the slow endothelialization of polycaprolactone vascular grafts implanted into a hypercholesterolemia rat model
复制标题
内皮细胞增殖、迁移和粘附能力受损与植入高胆固醇血症大鼠模型的聚己内酯血管移植物的缓慢内皮化有关
DOI：
10.1016/j.actbio.2022.06.048
复制
发表时间：
2022
影响因子：
9.7
通讯作者：
Xiaoyan Deng
中科院分区：
文献类型：
--
作者：
Hongyan Kang;Guiqin Yan;Weichen Zhang;Junwei Xu;Jiaxin Guo;Jiali Yang;Xiao Liu;Anqiang Sun;Zengsheng Chen;Yubo Fan;Xiaoyan Deng
大多数小直径血管移植物（内径<6 mm）评价研究是在不能代表临床情况的健康动物中进行的。在此，建立了高胆固醇血症（HC）大鼠模型，该模型具有内膜增厚和颈动脉分支中促炎细胞间粘附分子-1（ICAM-1）表达升高。将电纺聚己内酯（PCL）血管移植物（长度：1 cm;内径：2 mm）以端对端的方式植入HC大鼠腹主动脉中，并随访至43天，显示出相对较低的通畅率，伴有显著的新生内膜增生，丰富的胶原沉积，以及比植入健康血管中的血管移植物更慢的内皮化。此外，在静态和脉动流条件下评价，从HC血管分离的内皮细胞（EC）的增殖、迁移和粘附行为受损。HC主动脉内皮的DNA微阵列研究表明，参与EC增殖（Egr 2），凋亡（Zbtb 16和Mt 1）和代谢（Slc 7a 11和Hamp）的基因下调。这些结果提示，内皮细胞增殖、迁移和粘附能力的受损与移植物的不良性能有关。未来小直径血管移植物的临床前评价可能涉及更多具有临床并发症的疾病动物模型。在小直径血管移植物（D <6 mm）的开发过程中，优选从猪、羊、狗到兔和大鼠的年轻和健康的动物模型。然而，它不能代表临床情况，其中大多数心血管移植手术是在老年人中进行的，年龄是疾病发展或死亡的主要危险因素。在此，电纺聚己内酯（PCL）血管移植物植入高胆固醇血症（HC）或健康大鼠的性能进行了评价。结果表明，内皮细胞（EC）的增殖，迁移和粘附能力已经受损，在HC大鼠，这有助于观察到较慢的植入PCL移植物的内皮化。未来小直径血管移植物的临床前评价可能涉及更多具有临床并发症的疾病动物模型。
Most small diameter vascular grafts (inner diameter<6 mm) evaluation studies are performed in healthy animals that cannot represent the clinical situation. Herein, an hypercholesterolemia (HC) rat model with thickened intima and elevated expression of pro-inflammatory intercellular adhesion molecular-1 (ICAM-1) in the carotid branch is established. Electrospun polycaprolactone (PCL) vascular grafts (length: 1 cm; inner diameter: 2 mm) are implanted into the HC rat abdominal aortas in an end to end fashion and followed up to 43 days, showing a relative lower patency accompanied by significant neointima hyperplasia, abundant collagen deposition, and slower endothelialization than those implanted into healthy ones. Moreover, the proliferation, migration, and adhesion behavior of endothelial cells (ECs) isolated from the HC aortas are impaired as evaluated under both static and pulsatile flow conditions. DNA microarray studies of the HC aortic endothelium suggest genes involved in EC proliferation (Egr2), apoptosis (Zbtb16 and Mt1), and metabolism (Slc7a11 and Hamp) are down regulated. These results suggest the impaired proliferative, migratory, and adhesive abilities of ECs are associated with the bad performances of grafts in HC rat. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications. During the development of small diameter vascular grafts ( D <6 mm), young and healthy animal models from pigs, sheep, dogs, to rabbits and rats are preferred. However, it cannot represent the clinic situation, where most cardiovascular grafting procedures are performed in the elderly and age is the primary risk factor for disease development or death. Herein, the performance of electrospun polycaprolactone (PCL) vascular grafts implanted into hypercholesterolemia (HC) or healthy rats were evaluated. Results suggest the proliferative, migratory, and adhesive abilities of endothelial cells (ECs) are already impaired in HC rats, which contributes to the observed slower endothelialization of implanted PCL grafts. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications.