Department of Surgery, 6684Oregon Health and Science University, Portland, OR, USA.
Knight Cardiovascular Institute, 6684Oregon Health and Science University, Portland, OR, USA.
Vasc Endovascular Surg. 2022 Apr;56(3):244-252. doi: 10.1177/15385744211063054. Epub 2021 Dec 27.
Tobacco smoke exposure is a major risk factor for aortic aneurysm development. However, the initial aortic response to tobacco smoke, preceding aneurysm formation, is not well understood. We sought to create a model to determine the effect of solubilized tobacco smoke (STS) on the thoracic and abdominal aorta of mice as well as on cultured human aortic smooth muscle cells (HASMCs).
Tobacco smoke was solubilized and delivered to mice via implanted osmotic minipumps. Twenty male C57BL/6 mice received STS or vehicle infusion. The descending thoracic, suprarenal abdominal, and infrarenal abdominal segments of the aorta were assessed for elastic lamellar damage, smooth muscle cell phenotype, and infiltration of inflammatory cells. Cultured HASMCs grown in media containing STS were compared to cells grown in standard media in order to verify our in vivo findings.
Tobacco smoke solution caused significantly more breaks in the elastic lamellae of the thoracic and abdominal aorta compared to control solution (< .0001) without inciting an inflammatory infiltrate. Elastin breaks occurred more frequently in the abdominal aorta than the thoracic aorta ( < .01). Exposure to STS-induced aortic microdissections and downregulation of α-smooth muscle actin (α-SMA) by vascular smooth muscle cells (VSMCs). Treatment of cultured HASMCs with STS confirmed the decrease in α-SMA expression.
Delivery of STS via osmotic minipumps appears to be a promising model for investigating the early aortic response to tobacco smoke exposure. The initial effect of tobacco smoke exposure on the aorta is elastic lamellar damage and downregulation of (α-SMA) expression by VSMCs. Elastic lamellar damage occurs more frequently in the abdominal aorta than the thoracic aorta and does not seem to be mediated by the presence of macrophages or other inflammatory cells.
烟草烟雾暴露是主动脉瘤发展的一个主要危险因素。然而，烟草烟雾对主动脉的早期反应，即在动脉瘤形成之前，还没有得到很好的理解。我们试图建立一个模型，以确定可溶性烟草烟雾（STS）对小鼠胸主动脉和腹主动脉以及培养的人主动脉平滑肌细胞（HASMC）的影响。
烟草烟雾被溶解并通过植入的渗透微型泵输送给小鼠。20 只雄性 C57BL/6 小鼠接受 STS 或载体输注。胸主动脉的降段、肾上腺上腹部和肾下腹部以及腹主动脉的各段都进行了弹性层状损伤、平滑肌细胞表型和炎症细胞浸润的评估。与生长在标准培养基中的细胞相比，在含有 STS 的培养基中生长的培养 HASMCs 被用来验证我们的体内发现。
与对照溶液相比，烟草烟雾溶液导致胸主动脉和腹主动脉的弹性层状损伤明显增加（<.0001），而没有引起炎症浸润。弹性层状损伤在腹主动脉比在胸主动脉更常见（<.01）。暴露于 STS 会引起主动脉微夹层，并下调血管平滑肌细胞（VSMCs）中的α-平滑肌肌动蛋白（α-SMA）。用 STS 处理培养的 HASMCs 证实了 α-SMA 表达的减少。
通过渗透微型泵输送 STS 似乎是研究烟草烟雾暴露对主动脉早期反应的一个有前途的模型。烟草烟雾暴露对主动脉的最初影响是弹性层状损伤和 VSMCs 中（α-SMA）表达的下调。弹性层状损伤在腹主动脉比在胸主动脉更常见，似乎不是由巨噬细胞或其他炎症细胞的存在介导的。
