Emami Hamed, Singh Parmanand, MacNabb Megan, Vucic Esad, Lavender Zachary, Rudd James H F, Fayad Zahi A, Lehrer-Graiwer Joshua, Korsgren Magnus, Figueroa Amparo L, Fredrickson Jill, Rubin Barry, Hoffmann Udo, Truong Quynh A, Min James K, Baruch Amos, Nasir Khurram, Nahrendorf Matthias, Tawakol Ahmed
Cardiac MR PET CT Program, Division of Cardiac Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
JACC Cardiovasc Imaging. 2015 Feb;8(2):121-30. doi: 10.1016/j.jcmg.2014.10.009. Epub 2015 Jan 7.
This study sought to determine whether splenic activation after acute coronary syndrome (ACS) is linked to leukocyte proinflammatory remodeling and whether splenic activity independently predicts the risk of cardiovascular disease (CVD) events.
Pre-clinical data suggest the existence of a cardiosplenic axis, wherein activation of hematopoietic tissues (notably in the spleen) results in liberation of proinflammatory leukocytes and accelerated atherosclerotic inflammation. However, it is presently unknown whether a cardiosplenic axis exists in humans and whether splenic activation relates to CVD risk.
(18)F-fluorodeoxyglucose ((18)FDG)-positron emission tomography (PET) imaging was performed in 508 individuals across 2 studies. In the first study, we performed FDG-PET imaging in 22 patients with recent ACS and 22 control subjects. FDG uptake was measured in spleen and arterial wall, whereas proinflammatory gene expression of circulating leukocytes was assessed by quantitative real-time polymerase chain reaction. In a second study, we examined the relationship between splenic tissue FDG uptake with subsequent CVD events during follow-up (median 4 years) in 464 patients who previously had undergone FDG-PET imaging.
Splenic activity increased after ACS and was significantly associated with multiple indices of inflammation: 1) up-regulated gene expression of proinflammatory leukocytes; 2) increased C-reactive protein; and 3) increased arterial wall inflammation (FDG uptake). Moreover, in the second study, splenic activity (greater than or equal to the median) was associated with an increased risk of CVD events (hazard ratio [HR]: 3.3; 95% confidence interval [CI]: 1.5 to 7.3; p = 0.003), which remained significant after adjustment for CVD risk factors (HR: 2.26; 95% CI: 1.01 to 5.06; p = 0.04) and for arterial FDG uptake (HR: 2.68; 95% CI: 1.5 to 7.4; p = 0.02).
Our findings demonstrate increased splenic metabolic activity after ACS and its association with proinflammatory remodeling of circulating leukocytes. Moreover, we observed that metabolic activity of the spleen independently predicted risk of subsequent CVD events. Collectively, these findings provide evidence of a cardiosplenic axis in humans similar to that shown in pre-clinical studies.
本研究旨在确定急性冠脉综合征（ACS）后脾脏激活是否与白细胞促炎重塑相关，以及脾脏活动是否能独立预测心血管疾病（CVD）事件的风险。
临床前数据表明存在心脾轴，其中造血组织（特别是脾脏）的激活会导致促炎白细胞的释放和加速动脉粥样硬化炎症。然而，目前尚不清楚人类是否存在心脾轴，以及脾脏激活是否与CVD风险相关。
在两项研究中，对508名个体进行了（18）F-氟脱氧葡萄糖（（18）FDG）-正电子发射断层扫描（PET）成像。在第一项研究中，我们对22例近期ACS患者和22例对照者进行了FDG-PET成像。测量脾脏和动脉壁的FDG摄取，同时通过定量实时聚合酶链反应评估循环白细胞的促炎基因表达。在第二项研究中，我们检查了464例先前接受过FDG-PET成像的患者在随访期间（中位时间4年）脾脏组织FDG摄取与随后CVD事件之间的关系。
ACS后脾脏活动增加，且与多种炎症指标显著相关：1）促炎白细胞基因表达上调；2）C反应蛋白增加；3）动脉壁炎症（FDG摄取）增加。此外，在第二项研究中，脾脏活动（大于或等于中位数）与CVD事件风险增加相关（风险比[HR]：3.3；95%置信区间[CI]：1.5至7.3；p = 0.003），在调整CVD危险因素（HR：2.26；95%CI：1.01至5.06；p = 0.04）和动脉FDG摄取（HR：2.68；95%CI：1.5至7.4；p = 0.02）后仍具有显著性。
我们的研究结果表明ACS后脾脏代谢活性增加及其与循环白细胞促炎重塑的关联。此外，我们观察到脾脏的代谢活性独立预测随后CVD事件的风险。总体而言，这些发现提供了人类心脾轴与临床前研究中所示相似的证据。
