Rabkin Simon W
Department of Medicine, Division of Cardiology, University of British Columbia, Level 9 2775 Laurel St. Vancouver, B.C., Canada V5Z 1M9..
Curr Vasc Pharmacol. 2016;14(6):514-522. doi: 10.2174/1570161114666160625091205.
Aortic aneurysms (AAs) are without effective pharmacologic therapy, in clinical usage, in part because of the limited understanding of factors leading to AA development.
The objectives of this study were to examine the evidence that cigarette smoking induces AAs through altering matrix metalloproteinases (MMP) and the molecular biology/pharmacology that maybe involved in this effect.
A systematic search was conducted to identify studies that examined the links between cigarette smoke, MMP and AAs.
Eleven studies were identified. There was consistency, between studies. They found that cigarette smoke, nicotine or tobacco products increased aortic dimension and the proportion of AAs. Nicotine and tobacco constituents induced MMPs: MMP-1, MMP-2, MMP-8, MMP-9 and MMP-12 but with different levels of consistency. The molecular mechanisms involved in the pathogenesis of cigarette-induced AA formation, ranked according to the consistency of evidence include JNK, AMPK-α2, Jak Stat, and mTOR/p70Sk and PTEN pathways.
Nicotine and tobacco constituents translate the exposure to cigarette smoke into increased MMP expression through various molecular mechanisms whose interruption can form the basis for pharmacologic management of AAs.
主动脉瘤（AAs）目前尚无有效的药物治疗方法用于临床，部分原因是对导致主动脉瘤发生的因素了解有限。
本研究的目的是检验吸烟通过改变基质金属蛋白酶（MMP）诱导主动脉瘤发生的证据，以及可能参与此效应的分子生物学/药理学机制。
进行系统检索以识别研究吸烟、基质金属蛋白酶与主动脉瘤之间联系的研究。
共识别出11项研究。各研究之间具有一致性。他们发现，香烟烟雾、尼古丁或烟草制品会增加主动脉尺寸和主动脉瘤的比例。尼古丁和烟草成分可诱导基质金属蛋白酶：基质金属蛋白酶-1、基质金属蛋白酶-2、基质金属蛋白酶-8、基质金属蛋白酶-9和基质金属蛋白酶-12，但一致性程度不同。根据证据的一致性程度排列，吸烟诱导主动脉瘤形成的发病机制中涉及的分子机制包括JNK、AMPK-α2、Jak Stat以及mTOR/p70Sk和PTEN信号通路。
尼古丁和烟草成分通过各种分子机制将吸烟暴露转化为基质金属蛋白酶表达增加，阻断这些机制可为主动脉瘤的药物治疗奠定基础。
