Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Nature. 2012 Jul 19;487(7407):325-9. doi: 10.1038/nature11260.
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.
在动脉粥样硬化进展过程中，髓样细胞会使动脉壁中富含脂质的斑块不稳定并导致其破裂，从而引发心肌梗死和中风。急性冠脉综合征幸存者由于未知原因存在反复发作的高风险。在这里，我们表明，缺血性损伤的全身反应会加重慢性动脉粥样硬化。在心肌梗死或中风后，Apoe-/- 小鼠发展出更大的动脉粥样硬化病变，形态更为先进。这种疾病的加速持续了数周，并与单核细胞募集的明显增加有关。为了寻找斑块中多余单核细胞的来源，我们发现心肌梗死通过交感神经系统信号将造血干细胞和祖细胞从骨髓龛中释放出来。然后，这些祖细胞在脾脏中播种，导致单核细胞产生持续增加。这些观察结果为动脉粥样硬化的发病机制提供了新的机制见解，并为减轻疾病进展提供了新的治疗机会。
