ACE inhibitors potently reduce vascular inflammation, results of an open proof-of-concept study in the abdominal aortic aneurysm.
ACE inhibitors potently reduce vascular inflammation, results of an open proof-of-concept study in the abdominal aortic aneurysm.
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DOI：
10.1371/journal.pone.0111952
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lindeman JH
中科院分区：
文献类型：
--
作者：
Kortekaas KE;Meijer CA;Hinnen JW;Dalman RL;Xu B;Hamming JF;Lindeman JH
ACE抑制剂不依赖于它们的降血压作用，被认为可以减少血管炎症。根据目前的知识，该效应的临床相关性尚不清楚。腹主动脉瘤（AAA）的特点是广泛的，非特异性的炎症反应，因此提供了一个临床平台，以评估抗炎潜力的ACE抑制剂。11例计划进行开放式AAA修复术的患者在手术前2-4周接受了雷米普利（5 mg/天）。在手术过程中收集主动脉壁样本，并与从生物样本库获得的匹配样本进行比较。在包括免疫组织化学、mRNA和蛋白质分析的综合分析中评价抗炎潜力。通过比较服用ACE抑制剂（n = 82）和未服用ACE抑制剂（n = 204）的患者的18个月生长率，分别测试了ACE抑制剂对AAA生长的推定作用。 雷米普利降低多种促炎细胞因子如IL-1β、IL-6、IL-8、TNF -α、干扰素-α和MCP-1的mRNA表达，以及主动脉壁IL-8和MCP-1（分别为P=0.017和0.008）蛋白含量。 随后是对细胞活化的明显影响，包括向抗炎巨噬细胞（M2）亚型的转变。对PHAST队列数据的评价未表明ACE抑制剂对18个月动脉瘤进展的影响（18个月时的平均差异：−0.24 mm（95% CI：−0.90-0.45，P = NS）。 ACE抑制可抑制AAA血管炎症的多个方面。然而，这并不能转化为动脉瘤生长的减少。第1345章一夜情
Independent of their blood pressure lowering effect, ACE inhibitors are thought to reduce vascular inflammation. The clinical relevance of this effect is unclear with the current knowledge. Abdominal aortic aneurysms (AAA) are characterized by a broad, non-specific inflammatory response, and thus provide a clinical platform to evaluate the anti-inflammatory potential of ACE inhibitors. Eleven patients scheduled for open AAA repair received ramipril (5 mg/day) during 2–4 weeks preceding surgery. Aortic wall samples were collected during surgery, and compared to matched samples obtained from a biobank. An anti-inflammatory potential was evaluated in a comprehensive analysis that included immunohistochemistry, mRNA and protein analysis. A putative effect of ACE inhibitors on AAA growth was tested separately by comparing 18-month growth rate of patients on ACE inhibitors (n = 82) and those not taking ACE inhibitors (n = 204). Ramipril reduces mRNA expression of multiple pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF -α, Interferon-, and MCP-1, as well as aortic wall IL-8 and MCP-1 (P = 0.017 and 0.008, respectively) protein content. The is followed by clear effects on cell activation that included a shift towards anti-inflammatory macrophage (M2) subtype. Evaluation of data from the PHAST cohort did not indicate an effect of ACE inhibitors on 18-month aneurysm progression (mean difference at 18 months: −0.24 mm (95% CI: −0.90–0.45, P = NS). ACE inhibition quenches multiple aspects of vascular inflammation in AAA. However, this does not translate into reduced aneurysm growth. Nederlands Trial Register 1345.
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