Valatsou Angeliki, Theofilis Panagiotis, Simantiris Spyridon, Vogiatzi Georgia, Briasoulis Alexandros, Sagris Marios, Oikonomou Evangelos, Antonopoulos Alexios S, Pantopoulou Alkistis, Nasiri-Ansari Narjes, Fragopoulou Elizabeth, Perrea Despoina, Tsioufis Konstantinos, Tousoulis Dimitris
First Department of Cardiology, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece.
Third Department of Cardiology, Thoracic Diseases General Hospital "Sotiria", University of Athens Medical School, 11527 Athens, Greece.
Biomedicines. 2022 Sep 16;10(9):2303. doi: 10.3390/biomedicines10092303.
Novel therapies in peripheral arterial disease, such as granulocyte colony-stimulating factor (GCSF) administration, might result in anti-atherosclerotic effects. In this study, we used 10-week-old male ApoE mice, which were fed an atherosclerosis-inducing diet for four weeks. At the end of the four weeks, hind limb ischemia was induced through left femoral artery ligation, the atherosclerosis-inducing diet was discontinued, and a normal diet was initiated. Mice were then randomized into a control group (intramuscular 0.4 mL normal saline 0.9% for 7 days) and a group in which GCSF was administrated intramuscularly in the left hind limb for 7 days (100 mg/kg). In the GCSF group, but not in the control group, we observed significant reductions in the soluble adhesion molecules (vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1)), sE-Selectin, and plasminogen activator inhibitor (PAI)-1 when they were measured through ELISA on the 1st and the 28th days after hind limb ischemia induction. Therefore, GCSF administration in an atherosclerotic mouse model of hind limb ischemia led to decreases in the biomarkers associated with endothelial activation and thrombosis. These findings warrant further validation in future preclinical studies.
外周动脉疾病的新型疗法，如给予粒细胞集落刺激因子（GCSF），可能会产生抗动脉粥样硬化作用。在本研究中，我们使用了10周龄的雄性载脂蛋白E（ApoE）小鼠，给它们喂食致动脉粥样硬化饮食4周。在这4周结束时，通过结扎左股动脉诱导后肢缺血，停止致动脉粥样硬化饮食，并开始给予正常饮食。然后将小鼠随机分为对照组（肌肉注射0.4 mL 0.9%的生理盐水，共7天）和在左后肢肌肉注射GCSF 7天（100 mg/kg）的组。在GCSF组而非对照组中，在诱导后肢缺血后的第1天和第28天通过酶联免疫吸附测定（ELISA）测量时，我们观察到可溶性黏附分子（血管细胞黏附分子-1（sVCAM-1）和细胞间黏附分子-1（sICAM-1））、可溶性E-选择素和纤溶酶原激活物抑制剂（PAI）-1显著降低。因此，在动脉粥样硬化性后肢缺血小鼠模型中给予GCSF导致与内皮激活和血栓形成相关的生物标志物减少。这些发现值得在未来的临床前研究中进一步验证。
