Maguire Eithne M, Pearce Stuart W A, Xiao Rui, Oo Aung Y, Xiao Qingzhong
Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Barts Health NHS Trust and the Barts NIHR Biomedical Research Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Pharmaceuticals (Basel). 2019 Aug 6;12(3):118. doi: 10.3390/ph12030118.
Abdominal Aortic Aneurysm (AAA) affects 4-5% of men over 65, and Aortic Dissection (AD) is a life-threatening aortic pathology associated with high morbidity and mortality. Initiators of AAA and AD include smoking and arterial hypertension, whilst key pathophysiological features of AAA and AD include chronic inflammation, hypoxia, and large modifications to the extra cellular matrix (ECM). As it stands, only surgical methods are available for preventing aortic rupture in patients, which often presents difficulties for recovery. No pharmacological treatment is available, as such researchers are attempting to understand the cellular and molecular pathophysiology of AAA and AD. Upregulation of matrix metalloproteinase (MMPs), particularly MMP-2 and MMP-9, has been identified as a key event occurring during aneurysmal growth. As such, several animal models of AAA and AD have been used to investigate the therapeutic potential of suppressing MMP-2 and MMP-9 activity as well as modulating the activity of other MMPs, and TIMPs involved in the pathology. Whilst several studies have offered promising results, targeted delivery of MMP inhibition still needs to be developed in order to avoid surgery in high risk patients.
腹主动脉瘤(AAA)影响4%至5%的65岁以上男性,主动脉夹层(AD)是一种危及生命的主动脉病变,发病率和死亡率都很高。AAA和AD的引发因素包括吸烟和动脉高血压,而AAA和AD的关键病理生理特征包括慢性炎症、缺氧以及细胞外基质(ECM)的重大改变。目前,只有手术方法可用于预防患者的主动脉破裂,这往往给恢复带来困难。由于没有可用的药物治疗方法,因此研究人员正在试图了解AAA和AD的细胞和分子病理生理学。基质金属蛋白酶(MMPs),特别是MMP-2和MMP-9的上调,已被确定为动脉瘤生长过程中发生的关键事件。因此,几种AAA和AD动物模型已被用于研究抑制MMP-2和MMP-9活性以及调节参与该病理过程的其他MMPs和组织金属蛋白酶抑制剂(TIMPs)活性的治疗潜力。虽然几项研究已经取得了有希望的结果,但仍需要开发MMP抑制的靶向递送方法,以避免对高危患者进行手术。