Abdominal aortic aneurysm: novel mechanisms and therapies.
Abdominal aortic aneurysm: novel mechanisms and therapies.
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DOI：
10.1097/hco.0000000000000216
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发表时间：
2015-11
影响因子：
2.3
通讯作者：
Daugherty A
中科院分区：
文献类型：
--
作者：
Davis FM;Rateri DL;Daugherty A
腹主动脉瘤（AAA）是一种永久性扩张的病理状态，预示着主动脉破裂的潜在致命后果。这篇综述强调了动脉瘤发病机制和潜在药物治疗的最新进展。越来越多的证据表明，3p12.3、DAB 2 IP、LDLr、LRP 1、MMP 3、TGFβR2和SORT 1等基因位点与AAA的发生有关。目前的人体研究和动物模型表明，许多白细胞和炎症介质，如IL-1，IL-17，TGF-β和血管紧张素II，参与AAAs的发病机制。白细胞浸润至主动脉中膜导致平滑肌细胞耗竭、活性氧生成和细胞外基质断裂。最近对AAA药物治疗的临床前研究为microRNA调节AAA发展中许多病理途径的作用提供了有趣的见解。一些大型临床试验正在进行中，试图将临床前发现转化为治疗方案。最近的研究已经确定了AAA发病机制中涉及的许多潜在机制，为开发这种疾病的药物治疗提供了见解。
Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, MMP3, TGFβR2 and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Recent preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight for roles of microRNAs to regulate many pathological pathways in AAA development. Several large clinical trials are ongoing seeking to translate preclinical findings into therapeutic options. Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight for the development of a medical treatment for this disease.