Yin Jun, Zhao Chunguang, Huang Jiabing, Chen Changqing, Lei Ting, He Jiawei, Qiu Dongxu
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Critical Care Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan Province, China.
Acta Biomater. 2024 Mar 15;177:189-202. doi: 10.1016/j.actbio.2024.01.034. Epub 2024 Feb 1.
The endothelialization of drug-eluting stents is delayed after implantation in patients with diabetes. Although numerous factors were implicated in hyperglycemia-induced endothelial dysfunction, the effects of stent drug coating degradation on endothelial dysfunction remains unclear. We hypothesized that diabetic conditions promote drugcoating degradation and enhance antiproliferative agent release, but that the rapid release of these antiproliferative agents inhibits endothelial cell proliferation leading to poor reendothelialization post-stenting. To verify this hypothesis, a dynamic hyperglycemic circulation system was introduced to measure the profile of drugcoating degradation in vitro. Flow cytometry and RNA sequencing were performed to evaluate endothelial cell proliferation. Moreover, a Type 1 diabetic rabbit model was generated and a rescue experiment conducted to evaluate the effects of rapid drugcoating elution on endothelial coverage in vivo. The main findings were as follows: 1) diabetic conditions promoted drugcoating degradation and increased antiproliferative agent release; 2) this increase in antiproliferative agent release inhibited endothelial cell proliferation and delayed endothelial coverage; and 3) strict glycemic control attenuated drugcoating degradation and promoted endothelial coverage post-stenting. This is the first study to illustrate rapid drugcoating degradation and its potential effects on endothelial recovery under diabetic conditions, highlighting the importance of strict glycemic management in patients with diabetes after drug-eluting stent implantation. STATEMENT OF SIGNIFICANCE: Diabetic conditions promote drug coating degradation and increase the release of antiproliferative agents. Rapid drug coating degradation under diabetic conditions inhibits endothelial cell proliferation and delays endothelialization. Strict glycemic control attenuates drug coating degradation and promotes endothelialization.
药物洗脱支架植入糖尿病患者后，其内皮化过程会延迟。尽管高血糖诱导的内皮功能障碍涉及众多因素，但支架药物涂层降解对内皮功能障碍的影响仍不清楚。我们推测，糖尿病状态会促进药物涂层降解并增强抗增殖剂的释放，但这些抗增殖剂的快速释放会抑制内皮细胞增殖，导致支架置入后再内皮化不良。为了验证这一假设，引入了动态高血糖循环系统来体外测量药物涂层降解情况。进行了流式细胞术和RNA测序以评估内皮细胞增殖。此外，建立了1型糖尿病兔模型并进行了挽救实验，以评估快速药物涂层洗脱对体内内皮覆盖的影响。主要研究结果如下：1）糖尿病状态促进药物涂层降解并增加抗增殖剂释放；2）抗增殖剂释放的增加抑制了内皮细胞增殖并延迟了内皮覆盖；3）严格的血糖控制可减轻药物涂层降解并促进支架置入后的内皮覆盖。这是第一项阐述糖尿病状态下药物涂层快速降解及其对内皮恢复潜在影响的研究，突出了糖尿病患者药物洗脱支架植入后严格血糖管理的重要性。重要意义声明：糖尿病状态促进药物涂层降解并增加抗增殖剂的释放。糖尿病状态下药物涂层的快速降解抑制内皮细胞增殖并延迟内皮化。严格的血糖控制可减轻药物涂层降解并促进内皮化。
