Nature:心肌梗塞加重动脉粥样硬化进展

6月27日，Nature杂志在线报道了心肌梗塞加重动脉粥样硬化机制的最新进展。

在动脉粥样硬化的进展过程中，髓样细胞使富含脂质的动脉壁斑块不稳定，并导致其破裂，从而引发心肌梗塞和中风。由于尚不清楚的原因，急性冠脉综合征的幸存者具有高度复发风险。

本研究表明，缺血性损伤的系统性反应可加重慢性动脉粥样硬化。载脂蛋白E-/ -（Apoe-/-）小鼠心肌梗死或中风后，发生了更严重的，形态较大的动脉粥样硬化病变。这种疾病的恶化持续了几个星期，伴有显著增加的单核细胞聚集。

探求斑块中过剩的单核细胞的来源，研究者发现，心肌梗死通过交感神经系统的信号将造血干细胞和祖细胞从骨髓微环境中动员出来。这些造血祖细胞，随后接种到脾，产生持续增加的单核细胞生成。

这些观察到的现象为理解动脉粥样硬化的发生机制提供了新的线索，并为减轻病情进展，提供了一种新的治疗机会。

doi:10.1016/j.cell.2011.10.017
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Myocardial infarction accelerates atherosclerosis

Partha Dutta,1, 15 Gabriel Courties,1, 15 Ying Wei,2 Florian Leuschner,1, 3 Rostic Gorbatov,1 Clinton S. Robbins,1 Yoshiko Iwamoto,1 Brian Thompson,1 Alicia L. Carlson,1 Timo Heidt,1 Maulik D. Majmudar,1, 4 Felix Lasitschka,5 Martin Etzrodt,1 Peter Waterman,1 Michael T. Waring,6, 7 Adam T. Chicoine,6, 7 Anja M. van der Laan,8 Hans W. M. Niessen,9 Jan J. Piek,8 Barry B. Rubin,10 Jagdish Butany,11 James R. Stone,1, 12 Hugo A. Katus,3 Sabina A. Murphy,13 David A. Morrow,13
Marc S. Sabatine,13 Claudio Vinegoni,1 Michael A. Moskowitz,2
Mikael J. Pittet,1 Peter Libby,4 Charles P. Lin,1 Filip K. Swirski,1
Ralph Weissleder1, 14 & Matthias Nahrendorf1 et al.

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe?/? mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.