Traxler Denise, Hemetsberger Rayyan, Spannbauer Andreas, Zlabinger Katrin, Gugerell Alfred, Lukovic Dominika, Mandic Ljubica, Pavo Noemi, Winkler Johannes, Gyöngyösi Mariann
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Internal Medicine I - Cardiology, Nephrology, Intensive Care and Rhythmology, St. Johannes Hospital Dortmund, Dortmund, Germany.
Histol Histopathol. 2020 Jul;35(7):653-663. doi: 10.14670/HH-18-177. Epub 2019 Oct 24.
The incidence of in-stent restenosis (ISR) has declined dramatically, but once it develops, no current treatment option, such as drug-eluting stents, drug-coated balloons, or cutting balloons (CBs), prevents re-narrowing of the stented atherosclerotic artery. In this preclinical study, we aimed to improve the efficacy of ISR treatment by coating CBs with paclitaxel (paclitaxel-eluting cutting balloon; PECB) and to characterize the histological features of neo-ISRs that arise after ISR treatment. ISR was induced by bare metal stent (BMS) implantation in coronary arteries in pigs. After one month of follow-up, the BMS-induced ISR was treated with either CB or PECB. After another month, we performed quantitative coronary angiography, explanted the treated arteries and assessed histopathological and histomorphometric parameters. In addition, we compared the histological features of neo-ISRs with pre-treatment ISRs. Injury, inflammation, fibrin deposition, and endothelialization scores were similar between the CB and PECB groups at one month after ISR treatment. Neointimal area (0.87±0.61 vs. 1.95±1.14 mm², p=0.02), mean neointimal thickness (0.40±0.39 vs. 0.99±0.56 mm, p=0.01), and percent area stenosis (27.3±20.4 vs. 48.3±22.9%, p=0.04) were decreased in PECB-treated coronary arteries compared to CB-treated arteries, respectively. Density of cells (predominantly smooth muscle cells; SMCs) was increased in neo-ISRs (3.51±3.05×10³ vs. 6.35±2.57×10³ cells/mm², p<0.01), but significantly more CD68⁺ and CD20⁺ cells were found in the pre-treatment ISRs. In conclusion, PECB treatment of ISRs led to better results in terms of smaller neointimal area and %area stenosis of the neo-ISR. SMC density was increased in neo-ISRs in contrast with higher percentage of CD68⁺ and CD20⁺ cells in pre-treatment ISRs.
支架内再狭窄（ISR）的发生率已大幅下降，但一旦发生，目前的任何治疗方法，如药物洗脱支架、药物涂层球囊或切割球囊（CB），都无法防止支架置入的动脉粥样硬化动脉再次狭窄。在这项临床前研究中，我们旨在通过用紫杉醇包被CB（紫杉醇洗脱切割球囊；PECB）来提高ISR治疗的疗效，并描述ISR治疗后出现的新生内膜再狭窄的组织学特征。通过在猪冠状动脉中植入裸金属支架（BMS）诱导ISR。随访一个月后，用CB或PECB治疗BMS诱导的ISR。再过一个月，我们进行了定量冠状动脉造影，取出治疗的动脉并评估组织病理学和组织形态学参数。此外，我们比较了新生内膜再狭窄与治疗前ISR的组织学特征。ISR治疗后1个月，CB组和PECB组的损伤、炎症、纤维蛋白沉积和内皮化评分相似。与CB治疗的动脉相比，PECB治疗的冠状动脉的新生内膜面积（0.87±0.61 vs. 1.95±1.14 mm²，p=0.02）、平均新生内膜厚度（0.40±0.39 vs. 0.99±0.56 mm，p=0.01）和狭窄面积百分比（27.3±20.4 vs. 48.3±22.9%，p=0.04）均降低。新生内膜再狭窄中细胞（主要是平滑肌细胞；SMCs）密度增加（3.51±3.05×10³ vs. 6.35±2.57×10³ 个细胞/mm²，p<0.01），但在治疗前的ISR中发现CD68⁺和CD20⁺细胞明显更多。总之，PECB治疗ISR在新生内膜面积和新生内膜再狭窄的狭窄面积百分比方面产生了更好的结果。与治疗前ISR中较高百分比的CD68⁺和CD20⁺细胞相比，新生内膜再狭窄中的SMC密度增加。
