Center for Systems Biology, Massachusetts General Hospital, Boston, USA.
J Am Coll Cardiol. 2012 Jan 10;59(2):153-63. doi: 10.1016/j.jacc.2011.08.066.
The aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation.
Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the nonischemic remote zone recruits monocytes.
Acute inflammation was followed in mice with coronary ligation by 18-fluorodeoxyglucose ((18)FDG) positron emission tomography/magnetic resonance imaging, fluorescence-activated cell sorting, polymerase chain reaction, and histology.
Gd-DTPA-enhanced infarcts showed high (18)FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b(+) cells had 4-fold higher (18)FDG uptake than the infarct tissue from which they were isolated (p < 0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (approximately 10(4)/mg of myocardium, 5.6-fold increase; p < 0.01), a finding mirrored by macrophage infiltration in the remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative polymerase chain reaction showed a robust increase of recruiting adhesion molecules and chemokines in the remote myocardium (e.g., 12-fold increase of monocyte chemoattractant protein-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in noninfarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post-MI dilation.
This study shed light on the innate inflammatory response in remote myocardium after MI.
本研究旨在探讨心肌梗死后的心肌炎症。
先天免疫细胞在梗死愈合中起着核心作用，是心血管疾病中新兴的治疗靶点；然而，评估组织中其存在的临床工具却很匮乏。此外，目前尚不清楚非缺血性远隔区是否募集单核细胞。
通过 18-氟脱氧葡萄糖 ((18)FDG) 正电子发射断层扫描/磁共振成像、荧光激活细胞分选、聚合酶链反应和组织学，对冠状动脉结扎小鼠的急性炎症进行了后续研究。
Gd-DTPA 增强的梗死在 MI 后第 5 天显示出高 (18)FDG 摄取。细胞耗竭和分离数据证实，这主要反映了炎症；CD11b(+)细胞的 (18)FDG 摄取量比从其分离出的梗死组织高 4 倍（p < 0.01）。令人惊讶的是，远隔心肌有大量单核细胞募集（约 10(4)/mg 心肌，增加 5.6 倍；p < 0.01），这一发现与急性 MI 患者远隔心肌的巨噬细胞浸润相吻合。细胞募集的时间动力学比梗死更慢，缺血后第 10 天达到峰值。定量聚合酶链反应显示，远隔心肌中招募的黏附分子和趋化因子（例如单核细胞趋化蛋白-1 增加 12 倍）的表达显著增加，尽管水平始终低于梗死组织。最后，非梗死心肌中的基质金属蛋白酶活性显著增加，表明单核细胞向远隔区的募集可能导致 MI 后扩张。
本研究揭示了 MI 后远隔心肌的固有炎症反应。
