Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, 87036 Rende (CS), Italy.
Department of Experimental Medicine, Section of Pharmacology, University of Campania "Luigi Vanvitelli", 80138 Napoli, Italy.
Biomolecules. 2020 Feb 26;10(3):359. doi: 10.3390/biom10030359.
Matrix metalloproteinases (MMPs) are involved in vascular wall degradation, and drugs able to modulate MMP activity can be used to prevent or treat aneurysmal disease. In this study, we evaluated the effects of statins on MMP-2, MMP-9, and neutrophil gelatinase-associated lipocalin (NGAL) in both plasma and tissue in patients with aneurysmal disease.
We performed a prospective, single-blind, multicenter, control group clinical drug trial on 184 patients of both sexes >18 years old with a diagnosis of arterial aneurysmal disease. Enrolled patients were divided into two groups: Group I under statin treatment and Group II not taking statins. In addition, 122 patients without aneurysmal disease and under statin treatment were enrolled as a control group (Group III). The expression of MMPs and NGAL in plasma was evaluated using ELISA, while their expression in endothelial tissues was evaluated using Western blot.
The ELISA test revealed greater plasma levels ( < 0.01) of MMPs and NGAL in Groups I and II vs. Group III. Western blot analysis showed higher expression ( < 0.01) of MMPs and NGAL in Group II vs. Group I, and this increase was significantly higher ( < 0.01) in patients treated with low potency statins compared to high potency ones.
MMPs and NGAL seem to play a major role in the development of aneurysms, and their modulation by statins suggests that these drugs could be used to prevent arterial aneurysmal disease.
基质金属蛋白酶(MMPs)参与血管壁的降解,能够调节 MMP 活性的药物可用于预防或治疗动脉瘤疾病。在这项研究中,我们评估了他汀类药物对患有动脉瘤疾病的患者的血浆和组织中 MMP-2、MMP-9 和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的影响。
我们对 184 名年龄>18 岁的男女动脉动脉瘤疾病患者进行了一项前瞻性、单盲、多中心、对照组的临床药物试验。纳入的患者分为两组:他汀类药物治疗组(I 组)和未服用他汀类药物组(II 组)。此外,还纳入了 122 名无动脉瘤疾病且服用他汀类药物的患者作为对照组(III 组)。使用 ELISA 评估 MMPs 和 NGAL 在血浆中的表达,使用 Western blot 评估其在血管内皮组织中的表达。
ELISA 检测显示,I 组和 II 组患者的 MMPs 和 NGAL 血浆水平均较高(<0.01)。Western blot 分析显示,II 组的 MMPs 和 NGAL 表达较高(<0.01),且低效能他汀类药物治疗患者的增加幅度明显高于高效能他汀类药物治疗患者(<0.01)。
MMPs 和 NGAL 似乎在动脉瘤的发生发展中起重要作用,他汀类药物对其的调节作用提示这些药物可用于预防动脉动脉瘤疾病。