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Myocardial infarction accelerates atherosclerosis


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.

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Figure 1: Increased inflammation in atherosclerotic plaques after MI.
Figure 2: Elevated levels of progenitor cells in the spleen ofApoe−/− mice after MI.
Figure 3: β3-Adrenoceptor-mediated progenitor release after MI.
Figure 4: Serial intravital imaging of progenitor release from the bone marrow.
Figure 5: Splenic progenitor engraftment after MI.


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We thank the CSB Mouse Imaging Program (J. Truelove, D. Jeon, J. Donahoe, B. Marinelli) and K. Naxerova for helpful discussions. This work was funded by grants from the National Institute of Health R01-HL096576, R01-HL095629 (M.N.); R01-EB006432, T32-CA79443, P50-CA086355 (R.W.). F.L. was funded in part by Deutsche Forschungsgemeinschaft SFB 938/Z2. Fig. 5e was produced using Servier Medical Art (

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Authors and Affiliations



P.D. and G.C. performed experiments, collected and analysed the data, and contributed to writing the manuscript, R.G. did surgeries and performed experiments, Y.W., F.Le., R.G., C.S.R., Y.I., B.T., A.L.C., T.H., M.D.M., F.La., M.E., P.W., M.T.W., A.T.C., A.M.v.d.L., H.W.M.N., J.J.P., B.B.R., J.B., J.R.S., H.A.K., C.V., S.A.M., D.A.M. and M.S.S. performed experiments, collected, analysed and discussed data, M.A.M., M.J.P., P.L., C.P.L., F.K.S. and R.W. conceived experiments and discussed strategy and results; M.N. designed and managed the study and wrote the manuscript, which was edited and approved by all co-authors.

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Correspondence to Ralph Weissleder or Matthias Nahrendorf.

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Competing interests

M.S.S., D.A.M. and S.A.M. received grant support from AstraZeneca and GSK. The remaining authors declare no competing financial interests.

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Dutta, P., Courties, G., Wei, Y. et al. Myocardial infarction accelerates atherosclerosis. Nature 487, 325–329 (2012).

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