{"title":"半胱氨酸白三烯受体拮抗剂--孟鲁司特治疗可改善小鼠的实验性腹主动脉瘤","authors":"Kexin Li, Meng Li, Panpan Wei, Kangli Tian, Haole Liu, Weilai Fu, Haiwen Hou, Yajie Chen, Baohui Xu, Yankui Li, Sihai Zhao","doi":"10.1155/2024/8826287","DOIUrl":null,"url":null,"abstract":"<p><b>Background:</b> Cysteinyl leukotrienes (LTs) and their receptors are involved in the pathogenesis of abdominal aortic aneurysms (AAAs). However, whether CysLT1 receptor antagonists such as montelukast can influence experimental nondissecting AAA remains unclear.</p><p><b>Methods:</b> Nondissecting AAAs were induced in C57BL/6J mice by transient aortic luminal infusion of porcine pancreatic elastase (PPE). All animals were administrated montelukast (1 or 10 mg/kg, daily) or vehicle by gavage beginning 1 day before PPE infusion for 14 days. On day 0 (baseline) and day 14 after PPE infusion, abdominal aortic diameters were directly measured. Aortic aneurysmal segment samples were collected, and histopathological analysis was performed.</p><p><b>Results:</b> Compared to vehicle treatment, montelukast significantly decreased PPE infusion–induced aortic expansion in a dose-dependent manner (0.09-mm reduction at a low dose and 0.19-mm reduction at a high dose). Histopathological analysis also revealed that compared with vehicle treatment, montelukast treatment, especially in the high-dose group, significantly improved PPE-induced aortic elastin degradation and medial smooth muscle cell depletion. Both doses of montelukast also markedly decreased the number of local leucocytes, including macrophages, CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and B cells, infiltration and accumulation in aortic aneurysmal lesions. Montelukast treatment also downregulated matrix metalloproteinase 2 (MMP2) and MMP9 expression and inhibited mural angiogenesis in aneurysmal aortas.</p><p><b>Conclusion:</b> Montelukast treatment improves experimental nondissected AAAs in mice partly by improving aortic inflammation.</p>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/8826287","citationCount":"0","resultStr":"{\"title\":\"Cysteine Leukotriene Receptor Antagonist—Montelukast—Treatment Improves Experimental Abdominal Aortic Aneurysms in Mice\",\"authors\":\"Kexin Li, Meng Li, Panpan Wei, Kangli Tian, Haole Liu, Weilai Fu, Haiwen Hou, Yajie Chen, Baohui Xu, Yankui Li, Sihai Zhao\",\"doi\":\"10.1155/2024/8826287\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>Background:</b> Cysteinyl leukotrienes (LTs) and their receptors are involved in the pathogenesis of abdominal aortic aneurysms (AAAs). However, whether CysLT1 receptor antagonists such as montelukast can influence experimental nondissecting AAA remains unclear.</p><p><b>Methods:</b> Nondissecting AAAs were induced in C57BL/6J mice by transient aortic luminal infusion of porcine pancreatic elastase (PPE). All animals were administrated montelukast (1 or 10 mg/kg, daily) or vehicle by gavage beginning 1 day before PPE infusion for 14 days. On day 0 (baseline) and day 14 after PPE infusion, abdominal aortic diameters were directly measured. Aortic aneurysmal segment samples were collected, and histopathological analysis was performed.</p><p><b>Results:</b> Compared to vehicle treatment, montelukast significantly decreased PPE infusion–induced aortic expansion in a dose-dependent manner (0.09-mm reduction at a low dose and 0.19-mm reduction at a high dose). 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引用次数: 0
摘要
背景:半胱氨酰白三烯(LT)及其受体参与了腹主动脉瘤(AAA)的发病机制。然而,CysLT1受体拮抗剂(如孟鲁司特)能否影响实验性非解剖性AAA仍不清楚:方法:在 C57BL/6J 小鼠的主动脉腔内注入猪胰弹性蛋白酶(PPE),诱发非剥脱性 AAA。所有动物均在输注 PPE 前 1 天开始灌胃服用孟鲁司特(1 或 10 毫克/千克,每天)或药物,连续 14 天。在输注 PPE 后的第 0 天(基线)和第 14 天,直接测量腹主动脉直径。采集主动脉瘤节段样本,并进行组织病理学分析:结果:与药物治疗相比,孟鲁司特以剂量依赖的方式显著减少了PPE输注引起的主动脉扩张(低剂量减少0.09毫米,高剂量减少0.19毫米)。组织病理学分析还显示,与药物治疗相比,孟鲁司特治疗,尤其是在高剂量组,能显著改善 PPE 诱导的主动脉弹性蛋白降解和内侧平滑肌细胞耗竭。两种剂量的孟鲁司特还能明显减少主动脉瘤病变部位巨噬细胞、CD4+ T细胞、CD8+ T细胞和B细胞等局部白细胞的浸润和积聚。孟鲁司特治疗还能下调基质金属蛋白酶2(MMP2)和MMP9的表达,抑制动脉瘤主动脉壁血管生成:结论:孟鲁司特治疗可改善小鼠实验性非剥脱性 AAA,部分原因是改善了主动脉炎症。
Background: Cysteinyl leukotrienes (LTs) and their receptors are involved in the pathogenesis of abdominal aortic aneurysms (AAAs). However, whether CysLT1 receptor antagonists such as montelukast can influence experimental nondissecting AAA remains unclear.
Methods: Nondissecting AAAs were induced in C57BL/6J mice by transient aortic luminal infusion of porcine pancreatic elastase (PPE). All animals were administrated montelukast (1 or 10 mg/kg, daily) or vehicle by gavage beginning 1 day before PPE infusion for 14 days. On day 0 (baseline) and day 14 after PPE infusion, abdominal aortic diameters were directly measured. Aortic aneurysmal segment samples were collected, and histopathological analysis was performed.
Results: Compared to vehicle treatment, montelukast significantly decreased PPE infusion–induced aortic expansion in a dose-dependent manner (0.09-mm reduction at a low dose and 0.19-mm reduction at a high dose). Histopathological analysis also revealed that compared with vehicle treatment, montelukast treatment, especially in the high-dose group, significantly improved PPE-induced aortic elastin degradation and medial smooth muscle cell depletion. Both doses of montelukast also markedly decreased the number of local leucocytes, including macrophages, CD4+ T cells, CD8+ T cells, and B cells, infiltration and accumulation in aortic aneurysmal lesions. Montelukast treatment also downregulated matrix metalloproteinase 2 (MMP2) and MMP9 expression and inhibited mural angiogenesis in aneurysmal aortas.
Conclusion: Montelukast treatment improves experimental nondissected AAAs in mice partly by improving aortic inflammation.
期刊介绍:
Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged.
Subject areas include (but are by no means limited to):
Acute coronary syndrome
Arrhythmias
Atherosclerosis
Basic cardiac electrophysiology
Cardiac catheterization
Cardiac remodeling
Coagulation and thrombosis
Diabetic cardiovascular disease
Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF)
Hyperlipidemia
Hypertension
Ischemic heart disease
Vascular biology
Ventricular assist devices
Molecular cardio-biology
Myocardial regeneration
Lipoprotein metabolism
Radial artery access
Percutaneous coronary intervention
Transcatheter aortic and mitral valve replacement.