Cai Dunpeng, Chen Andy C, Zhou Ruimei, Murashita Takashi, Fay William P, Chen Shi-You
Departments of Surgery, University of Missouri School of Medicine, 1 Hospital Drive, Columbia, MO, 65212, USA.
The Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, 65212, USA.
Cardiovasc Drugs Ther. 2024 Jun 4. doi: 10.1007/s10557-024-07584-y.
The objective of the study is to test the efficacy of cyclopentenyl cytosine (CPEC)-coated stents on blocking artery stenosis, promoting reendothelialization, and reducing thrombosis.
Scanning electron microscopy was employed to observe the morphological characteristics of stents coated with a mixture of CPEC and poly(lactic-co-glycolic acid) (PLGA) copolymer. PLGA has been used in various Food and Drug Administration (FDA)-approved therapeutic devices. In vitro release of CPEC was tested to measure the dynamic drug elution. Comparison between CPEC- and everolimus-coated stents on neointimal formation and thrombosis formation was conducted after being implanted into the human internal mammary artery and grafted to the mouse aorta.
Optimization in stent coating resulted in uniform and consistent coating with minimal variation. In vitro drug release tests demonstrated a gradual and progressive discharge of CPEC. CPEC- or everolimus-coated stents caused much less stenosis than bare-metal stents. However, CPEC stent-implanted arteries exhibited enhanced reendothelialization compared to everolimus stents. Mechanistically, CPEC-coated stents reduced the proliferation of vascular smooth muscle cells while simultaneously promoting reendothelialization. More significantly, unlike everolimus-coated stents, CPEC-coated stents showed a significant reduction in thrombosis formation even in the absence of ongoing anticoagulant treatment.
The study establishes CPEC-coated stent as a promising new device for cardiovascular interventions. By enhancing reendothelialization and preventing thrombosis, CPEC offers advantages over conventional approaches, including the elimination of the need for anti-clogging drugs, which pave the way for improved therapeutic outcomes and management of atherosclerosis-related medical procedures.
本研究的目的是测试环戊烯基胞嘧啶(CPEC)涂层支架在阻止动脉狭窄、促进再内皮化和减少血栓形成方面的疗效。
采用扫描电子显微镜观察涂有CPEC与聚乳酸-羟基乙酸共聚物(PLGA)混合物的支架的形态特征。PLGA已用于各种获得美国食品药品监督管理局(FDA)批准的治疗器械。测试CPEC的体外释放以测量药物的动态洗脱。将CPEC涂层支架和依维莫司涂层支架植入人乳内动脉并移植到小鼠主动脉后,比较两者在新生内膜形成和血栓形成方面的差异。
支架涂层的优化导致涂层均匀一致,变化最小。体外药物释放测试表明CPEC呈逐渐且持续的释放。CPEC涂层支架或依维莫司涂层支架导致的狭窄比裸金属支架少得多。然而,与依维莫司支架相比,植入CPEC支架的动脉表现出更强的再内皮化。从机制上讲,CPEC涂层支架减少了血管平滑肌细胞的增殖,同时促进了再内皮化。更显著的是,与依维莫司涂层支架不同,即使在没有持续抗凝治疗的情况下,CPEC涂层支架的血栓形成也显著减少。
该研究确立了CPEC涂层支架作为一种有前景的心血管介入新器械。通过增强再内皮化和预防血栓形成,CPEC比传统方法具有优势,包括无需使用抗堵塞药物,这为改善治疗效果和管理动脉粥样硬化相关医疗程序铺平了道路。