PET/MRI of inflammation in myocardial infarction.

PET/MRI of inflammation in myocardial infarction.
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DOI:
10.1016/j.jacc.2011.08.066
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发表时间:
2012-01-10
影响因子:
24
通讯作者:
Nahrendorf, Matthias
Nahrendorf, Matthias
中科院分区:
医学1区
文献类型:
--
作者:
Lee, Won Woo;Marinelli, Brett;van der Laan, Anja M.;Sena, Brena F.;Gorbatov, Rostic;Leuschner, Florian;Dutta, Partha;Iwamoto, Yoshiko;Ueno, Takuya;Begieneman, Mark P. V.;Niessen, Hans W. M.;Piek, Jan J.;Vinegoni, Claudio;Pittet, Mikael J.;Swirski, Filip K.;Tawakol, Ahmed;Di Carli, Marcelo;Weissleder, Ralph;Nahrendorf, Matthias

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本研究的目的是探讨 MI 后心肌炎症。然而,先天免疫细胞主要参与梗塞愈合,并且是心血管疾病的新兴治疗靶点。评估它们在组织中存在的临床工具很少。此外,目前尚不清楚非缺血性远端区域是否募集单核细胞。通过 18FDG PET/MRI、FACS、PCR 和组织学追踪冠状动脉结扎小鼠的急性炎症。 Gd-DTPA 增强的梗塞在 MI 后第 5 天显示出高 18FDG 摄取。细胞消耗和分离数据证实这在很大程度上反映了炎症; CD11b + 细胞的 18FDG 摄取量比其分离的梗塞组织高 4 倍(P<0.01)。令人惊讶的是,远端心肌中有大量单核细胞募集(~104/mg心肌,增加5.6倍,P<0.01),急性心肌梗死患者远端心肌中的巨噬细胞浸润也反映了这一发现。细胞募集的时间动力学比梗塞时慢,在缺血后第 10 天达到峰值。定量 PCR 显示远端心肌中募集粘附分子和趋化因子的强劲增加(例如 MCP-1 增加 12 倍),尽管其水平始终低于梗死部位。最后,非梗塞心肌中基质金属蛋白酶活性显着增加,表明单核细胞募集到远端区域可能有助于心肌梗塞后扩张。这些研究揭示了心肌梗塞后远端心肌的先天炎症反应。
The aim of this study was to explore post-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 non-ischemic remote zone recruits monocytes. Acute inflammation was followed in mice with coronary ligation by 18FDG PET/MRI, FACS, PCR and histology. Gd-DTPA enhanced infarcts showed high 18FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b+ cells had 4-fold higher 18FDG uptake than the infarct tissue from which they were isolated (P<0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (~104/mg myocardium, 5.6-fold increase, P<0.01), a finding mirrored by macrophage infiltration in 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 PCR showed robust increase of recruiting adhesion molecules and chemokines in remote myocardium (e.g. 12-fold increase of MCP-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in non-infarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post MI dilation. These studies shed light on the innate inflammatory response in remote myocardium after myocardial infarction.
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