Splenic metabolic activity predicts risk of future cardiovascular events: demonstration of a cardiosplenic axis in humans.
Splenic metabolic activity predicts risk of future cardiovascular events: demonstration of a cardiosplenic axis in humans.
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DOI：
10.1016/j.jcmg.2014.10.009
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Tawakol A
中科院分区：
文献类型：
--
作者：
Emami H;Singh P;MacNabb M;Vucic E;Lavender Z;Rudd JH;Fayad ZA;Lehrer-Graiwer J;Korsgren M;Figueroa AL;Fredrickson J;Rubin B;Hoffmann U;Truong QA;Min JK;Baruch A;Nasir K;Nahrendorf M;Tawakol A
在这项研究中，我们试图确定：1）急性冠状动脉综合征（ACS）后的脾脏激活是否与白细胞促炎症重塑有关，以及2）脾脏活动是否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（特别是在脾中）的活化导致促炎性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：1）人类是否存在心脾轴，以及2）脾脏激活是否与CVD风险有关。在两项研究中对508名个体进行了18FDG-PET成像。在第一项研究中，我们对22名近期ACS患者和22名对照者进行了FDG-PET成像。测量脾脏和动脉壁中的FDG摄取，同时通过qRT-PCR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例既往接受过FDG-PET成像的患者在随访期间（中位数4年）脾组织FDG摄取与随后CVD事件之间的关系。ACS后脾脏活动增加，并与多种炎症指标显著相关：a）促炎性白细胞的基因表达上调，B）C反应蛋白增加，c）动脉壁炎症（FDG摄取）增加。此外，在第二项研究中，脾脏活动（≥中位数）与CVD事件风险增加相关（HR [95% CI] =3.3 [1.5，7.3]，p=0.003），在调整CVD风险因素后仍具有显著性（HR = 2.26 [1.01，5.06]，p=0.04）和动脉FDG摄取（HR=2.68 [1.5-7.4]，p=0.02）。我们的研究结果表明ACS后脾脏代谢活性增加，并与循环白细胞的促炎性重塑相关。此外，我们观察到脾脏的代谢活动独立预测随后的CVD事件的风险。总的来说，这些发现提供了与临床前研究中所示相似的人类心脾轴的证据。临床前数据表明存在心脾轴，其中造血组织（特别是脾）的激活导致促炎性白细胞的释放和加速动脉粥样硬化。我们试图确定ACS后脾脏激活是否与白细胞重塑有关，以及脾脏活动是否预测心血管事件的风险。我们在近期ACS患者中进行了18FDG-PET成像。在第二项研究中，我们检查了脾脏FDG摄取与随后心血管事件之间的关系。我们的研究结果表明ACS后脾脏代谢活性增加及其与促炎性白细胞的相关性。此外，我们观察到脾脏活动独立预测后续事件的风险。
In this study, we sought to determine: 1) whether splenic activation after acute coronary syndrome (ACS) is linked to leukocyte pro-inflammatory remodeling, and 2) whether splenic activity independently predicts the risk of cardiovascular disease (CVD) events. Preclinical data suggest the existence of a cardiosplenic axis, wherein activation of hematopoietic tissues (notably in the spleen) results in liberation of pro-inflammatory leukocytes and accelerated atherosclerotic inflammation. However, it is presently unknown whether: 1) a cardiosplenic axis exists in humans, and 2) whether splenic activation relates to CVD risk. 18FDG-PET imaging was performed in 508 individuals across two studies. In the first study we performed FDG-PET imaging in 22 patients with recent ACS and 22 controls. FDG uptake was measured in spleen and arterial wall while pro-inflammatory gene expression of circulating leukocytes was assessed by qRT-PCR. 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: a) up-regulated gene expression of pro-inflammatory leukocytes, b) increased C-reactive protein, and c) increased arterial wall inflammation (FDG uptake). Moreover, in the second study, splenic activity (≥median) was associated with increased risk of CVD events (HR [95% CI] =3.3 [1.5, 7.3], p=0.003) which remained significant after adjustment for CVD risk factors (HR = 2.26 [1.01, 5.06], p=0.04) and for arterial FDG uptake (HR=2.68 [1.5–7.4], p=0.02). Our findings demonstrate increased splenic metabolic activity after ACS and its association with pro-inflammatory remodeling of circulating leukocytes. Moreover, we observe that metabolic activity of the spleen independently predicts risk of subsequent CVD events. Collectively, these findings provide evidence of a cardiosplenic axis in humans similar to that shown in preclinical studies. Preclinical data suggest the existence of a cardiosplenic axis, wherein activation of hematopoietic tissues (especially spleen) results in liberation of pro-inflammatory leukocytes and accelerated atherosclerosis. We sought to determine whether splenic activation after ACS is linked to leukocyte remodeling, and whether splenic activity predicts the risk of cardiovascular events. We performed 18FDG-PET imaging in individuals with recent ACS. In a second study, we examined the relationship between splenic FDG uptake and subsequent cardiovascular events. Our findings demonstrate increased splenic metabolic activity post-ACS and its association with pro-inflammatory leukocytes. Moreover, we observed that spleen activity independently predicts risk of subsequent events.
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影响因子：
20.1
作者：
Ismahil MA;Hamid T;Bansal SS;Patel B;Kingery JR;Prabhu SD
通讯作者：
Prabhu SD
影响因子：
37.8
作者：
Croce K;Gao H;Wang Y;Mooroka T;Sakuma M;Shi C;Sukhova GK;Packard RR;Hogg N;Libby P;Simon DI
通讯作者：
Simon DI
DOI：
10.1161/circimaging.113.001093
发表时间：
2014-05-01
期刊：
Circulation. Cardiovascular imaging
影响因子：
--
作者：
Kim, Eung Ju;Kim, Sungeun;Seo, Hong Seog
通讯作者：
Seo, Hong Seog
动脉粥样硬化的炎症。
DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Libby P
通讯作者：
Libby P
影响因子：
5.2
作者：
Pittet MJ;Nahrendorf M;Swirski FK
通讯作者：
Swirski FK