Kunio Mie, Wong Gee, Markham Peter M, Edelman Elazer R
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
CBSET, Inc., Lexington, Massachusetts, United States of America.
PLoS One. 2018 Jan 29;13(1):e0192004. doi: 10.1371/journal.pone.0192004. eCollection 2018.
Sex-related differences have been noted in cardiovascular anatomy, pathophysiology, and treatment responses, yet we continued to drive evaluation of vascular device development in animal models without consideration of animal sex. We aimed to understand sex-related differences in the vascular responses to stent implantation by analyzing the pooled data of endovascular interventions in 164 Yucatan mini-swine (87 female, 77 male). Bare metal stents (BMS) or drug-eluting stents (DES) were implanted in 212 coronary arteries (63 single BMS implantation, 68 single DES implantation, 33 overlapped BMS implantation, and 48 overlapped DES implantation). Histomorphological parameters were evaluated from vascular specimens at 3-365 days after stent implantation and evaluated values were compared between female and male groups. While neointima formation at all times after implantation was invariant to sex, statistically significant differences between female and male groups were observed in injury, inflammation, adventitial fibrosis, and neointimal fibrin deposition. These differences were observed independently, i.e., for different procedure types and at different follow-up timings. Only subtle temporal sex-related differences were observed in extent and timing of resolution of inflammation and fibrin clearance. These subtle sex-related differences may be increasingly important as interventional devices meld novel materials that erode and innovations in drug delivery. Erodible materials may act differently if inflammation has a different temporal sequence with sex, and drug distribution after balloon or stent delivery might be different if the fibrin clearance speaks to different modes of pharmacokinetics in male and female swine.
心血管解剖学、病理生理学及治疗反应方面已发现性别差异，但我们在动物模型中对血管装置开发进行评估时，仍未考虑动物性别。我们旨在通过分析164只尤卡坦小型猪（87只雌性，77只雄性）血管内介入治疗的汇总数据，了解支架植入后血管反应的性别差异。在212条冠状动脉中植入裸金属支架（BMS）或药物洗脱支架（DES）（63例单BMS植入、68例单DES植入、33例重叠BMS植入和48例重叠DES植入）。在支架植入后3至365天从血管标本评估组织形态学参数，并比较雌性和雄性组的评估值。虽然植入后所有时间的新生内膜形成与性别无关，但在损伤、炎症、外膜纤维化和新生内膜纤维蛋白沉积方面，雌性和雄性组之间观察到统计学上的显著差异。这些差异是独立观察到的，即在不同的手术类型和不同的随访时间。在炎症消退程度和时间以及纤维蛋白清除方面，仅观察到细微的与性别相关的时间差异。随着介入装置融合新型可侵蚀材料和药物递送方面的创新，这些细微的性别相关差异可能变得越来越重要。如果炎症在性别上有不同的时间序列，可侵蚀材料的作用可能会有所不同；如果纤维蛋白清除表明雄性和雌性猪的药代动力学模式不同，球囊或支架递送后的药物分布可能也会不同。
