Hurks Rob, Vink Aryan, Hoefer Imo E, de Vries Jean-Paul P M, Schoneveld Arjan H, Schermerhorn Marc L, den Ruijter Hester M, Pasterkamp Gerard, Moll Frans L
Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Pathology, University Medical Center Utrecht, Room H04.312, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Atherosclerosis. 2014 Aug;235(2):632-41. doi: 10.1016/j.atherosclerosis.2014.05.928. Epub 2014 Jun 13.
Evidence is emerging that abdominal aortic aneurysm (AAA) formation cannot completely be explained by systemic atherosclerosis and is in part due to other pathophysiological mechanisms such as local immune reactions. The aim of the present study was to study variance in AAA wall inflammation, and relate that to clinical patient characteristics.
Ventral walls from 201 patients with intact AAAs undergoing open repair were prospectively collected and processed for histology and protein measurements. Patients were monitored for 3 years postoperatively.
The amount of lymphocytic infiltrate was used to distinguish 96 lymphocyte-poor AAAs from 105 lymphocyte-rich AAAs. The walls of lymphocyte-rich AAAs had higher concentrations of various inflammatory markers, including interleukin (IL) 6, IL8, matrix metalloproteinase (MMP) 8; however, MMP9 levels were comparable. Patients with lymphocyte-poor AAAs had more atherosclerotic risk factors: type 2 diabetes (22% vs. 9%, P = .008), hypertension (81% vs 66%, P = .019), and serum cholesterol levels (mean[SD] 5.2[2.5] vs. 4.2[1.0] mmol/L, P = .023). Intimal lesions in the AAAs revealed more frequently an extracellular lipid pool in lymphocyte-poor AAAs (66% vs. 52%, P = .026). Lymphocyte poor AAAs were associated with a worse survival during 3 years of follow-up, although this association did not reach statistical significance when correcting for other cardiovascular predictors (24% vs. 14%; HR 1.9-2.3).
Low amount of inflammation in AAAs is associated with more atherosclerotic risk factors, more advanced local atherosclerotic lesions and more postoperative atherosclerotic adverse events. This observation supports the view that AAA development is a multi-factorial process in which part of the patient population has a closer relation with systemic atherosclerotic disease, while in other patients local inflammatory reactions might play a larger role.
越来越多的证据表明,腹主动脉瘤(AAA)的形成不能完全用全身性动脉粥样硬化来解释,部分原因是其他病理生理机制,如局部免疫反应。本研究的目的是研究AAA壁炎症的差异,并将其与临床患者特征相关联。
前瞻性收集201例接受开放修复的完整AAA患者的腹主动脉前壁,进行组织学和蛋白质测量。对患者进行术后3年的监测。
淋巴细胞浸润量用于区分96例淋巴细胞少的AAA和105例淋巴细胞多的AAA。淋巴细胞多的AAA壁中各种炎症标志物的浓度较高,包括白细胞介素(IL)6、IL8、基质金属蛋白酶(MMP)8;然而,MMP9水平相当。淋巴细胞少的AAA患者有更多的动脉粥样硬化危险因素:2型糖尿病(22%对9%,P = 0.008)、高血压(81%对66%,P = 0.019)和血清胆固醇水平(均值[标准差]5.2[2.5]对4.2[1.0]mmol/L,P = 0.023)。AAA的内膜病变在淋巴细胞少的AAA中更频繁地显示细胞外脂质池(66%对52%,P = 0.026)。淋巴细胞少的AAA与随访3年期间较差的生存率相关,尽管在校正其他心血管预测因素后这种关联未达到统计学意义(24%对14%;风险比1.9 - 2.3)。
AAA中炎症程度低与更多的动脉粥样硬化危险因素、更严重的局部动脉粥样硬化病变和更多的术后动脉粥样硬化不良事件相关。这一观察结果支持了AAA发展是一个多因素过程的观点,其中部分患者群体与全身性动脉粥样硬化疾病关系更密切,而在其他患者中局部炎症反应可能起更大作用。