Calfon Press Marcella A, Mallas Georgios, Rosenthal Amir, Hara Tetsuya, Mauskapf Adam, Nudelman R Nika, Sheehy Alexander, Polyakov Igor V, Kolodgie Frank, Virmani Renu, Guerrero J Luis, Ntziachristos Vasilis, Jaffer Farouc A
Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.
Department of Cardiology, Ronald Reagan Medical Center, University of California in Los Angeles, Los Angeles CA, USA.
Eur Heart J Cardiovasc Imaging. 2017 May 1;18(5):510-518. doi: 10.1093/ehjci/jew228.
Inflammation drives atherosclerosis complications and is a promising therapeutic target for plaque stabilization. At present, it is unknown whether local stenting approaches can stabilize plaque inflammation in vivo. Here, we investigate whether everolimus-eluting stents (EES) can locally suppress plaque inflammatory protease activity in vivo using intravascular near-infrared fluorescence (NIRF) molecular imaging.
Balloon-injured, hyperlipidaemic rabbits with atherosclerosis received non-overlapping EES and bare metal stents (BMS) placement into the infrarenal aorta (n = 7 EES, n = 7 BMS, 3.5 mm diameter x 12 mm length). Four weeks later, rabbits received an injection of the cysteine protease-activatable NIRF imaging agent Prosense VM110. Twenty-four hours later, co-registered intravascular 2D NIRF, X-ray angiography and intravascular ultrasound imaging were performed. In vivo EES-stented plaques contained substantially reduced NIRF inflammatory protease activity compared with untreated plaques and BMS-stented plaques (P = 0.006). Ex vivo macroscopic NIRF imaging of plaque protease activity corroborated the in vivo results (P = 0.003). Histopathology analyses revealed that EES-treated plaques showed reduced neointimal and medial arterial macrophage and cathepsin B expression compared with unstented and BMS-treated plaques.
EES-stenting stabilizes plaque inflammation as assessed by translational intravascular NIRF molecular imaging in vivo. These data further support that EES may provide a local approach for stabilizing inflamed plaques.
炎症驱动动脉粥样硬化并发症，是斑块稳定化的一个有前景的治疗靶点。目前，尚不清楚局部支架置入方法能否在体内稳定斑块炎症。在此，我们使用血管内近红外荧光（NIRF）分子成像研究依维莫司洗脱支架（EES）是否能在体内局部抑制斑块炎症蛋白酶活性。
对患有动脉粥样硬化的球囊损伤高脂血症兔，在肾下主动脉置入非重叠的EES和裸金属支架（BMS）（n = 7个EES，n = 7个BMS，直径3.5 mm×长度12 mm）。四周后，给兔子注射半胱氨酸蛋白酶可激活的NIRF成像剂Prosense VM110。24小时后，进行血管内二维NIRF、X射线血管造影和血管内超声成像的联合注册。与未治疗的斑块和BMS置入的斑块相比，体内EES置入的斑块中NIRF炎症蛋白酶活性显著降低（P = 0.006）。斑块蛋白酶活性的体外宏观NIRF成像证实了体内结果（P = 0.003）。组织病理学分析显示，与未置入支架和BMS治疗的斑块相比，EES治疗的斑块内膜和中膜动脉巨噬细胞及组织蛋白酶B表达减少。
通过体内转化血管内NIRF分子成像评估，EES置入可稳定斑块炎症。这些数据进一步支持EES可能为稳定炎症斑块提供一种局部方法。
