Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
J Am Coll Cardiol. 2018 Jan 23;71(3):263-275. doi: 10.1016/j.jacc.2017.11.024.
The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration.
This study sought to assess the influence of MI on cardiac and brain inflammation using noninvasive positron emission tomography (PET) of the heart-brain axis.
After coronary artery ligation or sham surgery, mice (n = 49) underwent serial whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a marker of activated macrophages and microglia. Patients after acute MI (n = 3) were also compared to healthy controls (n = 9).
Infarct mice exhibited elevated myocardial TSPO signal at 1 week versus sham (percent injected dose per gram: 8.0 ± 1.6 vs. 4.8 ± 0.9; p < 0.001), localized to activated CD68 inflammatory cells in the infarct. Early TSPO signal predicted subsequent left ventricular remodeling at 8 weeks (r = -0.687; p = 0.001). In parallel, brain TSPO signal was elevated at 1 week (1.7 ± 0.2 vs. 1.4 ± 0.2 for sham; p = 0.017), localized to activated microglia. After interval decline at 4 weeks, progressive heart failure precipitated a second wave of neuroinflammation (1.8 ± 0.2; p = 0.005). TSPO was concurrently up-regulated in remote cardiomyocytes at 8 weeks (8.8 ± 1.7, p < 0.001) without inflammatory cell infiltration, suggesting mitochondrial impairment. Angiotensin-converting enzyme inhibitor treatment lowered acute inflammation in the heart (p = 0.003) and brain (p = 0.06) and improved late cardiac function (p = 0.05). Patients also demonstrated elevation of cardiac TSPO signal in the infarct territory, paralleled by neuroinflammation versus controls.
The brain is susceptible to acute MI and chronic heart failure. Immune activation may interconnect heart and brain dysfunction, a finding that provides a foundation for strategies to improve heart and brain outcomes.
急性心肌梗死（MI）后局部炎症组织反应决定了随后的愈合情况。全身相互作用可能会引发神经炎症，作为神经退行性变的前兆。
本研究旨在使用心脏-大脑轴的非侵入性正电子发射断层扫描（PET）评估 MI 对心脏和大脑炎症的影响。
在冠状动脉结扎或假手术后，对小鼠（n=49）进行心脏大脑轴线粒体转位蛋白（TSPO）的连续全身 PET 成像，作为激活的巨噬细胞和小胶质细胞的标志物。还将急性 MI 后的患者（n=3）与健康对照（n=9）进行比较。
与假手术相比，梗死小鼠在 1 周时表现出心肌 TSPO 信号升高（每克注射剂量的百分比：8.0±1.6 对 4.8±0.9；p<0.001），定位在梗死处的激活 CD68 炎性细胞中。早期 TSPO 信号预测 8 周时左心室重构（r=-0.687；p=0.001）。同时，在 1 周时大脑 TSPO 信号升高（1.7±0.2 对假手术 1.4±0.2；p=0.017），定位在激活的小胶质细胞中。4 周时信号下降后，进行性心力衰竭引发了第二次神经炎症（1.8±0.2；p=0.005）。在 8 周时，远程心肌细胞中 TSPO 也同时上调（8.8±1.7，p<0.001），而无炎性细胞浸润，提示线粒体损伤。血管紧张素转换酶抑制剂治疗降低了心脏（p=0.003）和大脑（p=0.06）的急性炎症，并改善了晚期心脏功能（p=0.05）。患者还表现出梗死区域心脏 TSPO 信号升高，与对照组相比，同时伴有神经炎症。
大脑易受急性 MI 和慢性心力衰竭的影响。免疫激活可能会使心脏和大脑功能障碍相互关联，这一发现为改善心脏和大脑预后的策略提供了基础。
