Myocardial infarction accelerates atherosclerosis

P. Dutta, G. Courties, Y. Wei, F. Leuschner, R. Gorbatov, C.S. Robbins, Y. Iwamoto, B. Thompson, A.L. Carlson, T. Heidt, M.D. Majmudar, F. Lasitschka, M. Etzrodt, P. Waterman, M.T. Waring, A.T. Chicoine, A.M. van der Laan, H.W.M. Niessen, J.J. Piek, B.B. Rubin & 14 others J. Butany, J.R. Stone, H.A. Katus, S.A. Murphy, D.A. Morrow, M.S. Sabatine, C. Vinegoni, M.A. Moskowitz, M.J. Pittet, P. Libby, C.P. Lin, F.K. Swirski, R. Weissleder, M. Nahrendorf

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)325-329
Number of pages5
JournalNature
Volume487
Issue number7407
DOIs
Publication statusPublished - 19 Jul 2012

Cite this

Dutta, P., Courties, G., Wei, Y., Leuschner, F., Gorbatov, R., Robbins, C. S., ... Nahrendorf, M. (2012). Myocardial infarction accelerates atherosclerosis. Nature, 487(7407), 325-329. https://doi.org/10.1038/nature11260
Dutta, P. ; Courties, G. ; Wei, Y. ; Leuschner, F. ; Gorbatov, R. ; Robbins, C.S. ; Iwamoto, Y. ; Thompson, B. ; Carlson, A.L. ; Heidt, T. ; Majmudar, M.D. ; Lasitschka, F. ; Etzrodt, M. ; Waterman, P. ; Waring, M.T. ; Chicoine, A.T. ; van der Laan, A.M. ; Niessen, H.W.M. ; Piek, J.J. ; Rubin, B.B. ; Butany, J. ; Stone, J.R. ; Katus, H.A. ; Murphy, S.A. ; Morrow, D.A. ; Sabatine, M.S. ; Vinegoni, C. ; Moskowitz, M.A. ; Pittet, M.J. ; Libby, P. ; Lin, C.P. ; Swirski, F.K. ; Weissleder, R. ; Nahrendorf, M. / Myocardial infarction accelerates atherosclerosis. In: Nature. 2012 ; Vol. 487, No. 7407. pp. 325-329.
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title = "Myocardial infarction accelerates atherosclerosis",
abstract = "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.",
keywords = "Animals, Apolipoproteins E, Atherosclerosis, Hematopoietic Stem Cells, Inflammation, Mice, Mice, Inbred C57BL, Monocytes, Myocardial Infarction, Spleen, Stem Cells, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
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Dutta, P, Courties, G, Wei, Y, Leuschner, F, Gorbatov, R, Robbins, CS, Iwamoto, Y, Thompson, B, Carlson, AL, Heidt, T, Majmudar, MD, Lasitschka, F, Etzrodt, M, Waterman, P, Waring, MT, Chicoine, AT, van der Laan, AM, Niessen, HWM, Piek, JJ, Rubin, BB, Butany, J, Stone, JR, Katus, HA, Murphy, SA, Morrow, DA, Sabatine, MS, Vinegoni, C, Moskowitz, MA, Pittet, MJ, Libby, P, Lin, CP, Swirski, FK, Weissleder, R & Nahrendorf, M 2012, 'Myocardial infarction accelerates atherosclerosis' Nature, vol. 487, no. 7407, pp. 325-329. https://doi.org/10.1038/nature11260

Myocardial infarction accelerates atherosclerosis. / Dutta, P.; Courties, G.; Wei, Y.; Leuschner, F.; Gorbatov, R.; Robbins, C.S.; Iwamoto, Y.; Thompson, B.; Carlson, A.L.; Heidt, T.; Majmudar, M.D.; Lasitschka, F.; Etzrodt, M.; Waterman, P.; Waring, M.T.; Chicoine, A.T.; van der Laan, A.M.; Niessen, H.W.M.; Piek, J.J.; Rubin, B.B.; Butany, J.; Stone, J.R.; Katus, H.A.; Murphy, S.A.; Morrow, D.A.; Sabatine, M.S.; Vinegoni, C.; Moskowitz, M.A.; Pittet, M.J.; Libby, P.; Lin, C.P.; Swirski, F.K.; Weissleder, R.; Nahrendorf, M.

In: Nature, Vol. 487, No. 7407, 19.07.2012, p. 325-329.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Myocardial infarction accelerates atherosclerosis

AU - Dutta, P.

AU - Courties, G.

AU - Wei, Y.

AU - Leuschner, F.

AU - Gorbatov, R.

AU - Robbins, C.S.

AU - Iwamoto, Y.

AU - Thompson, B.

AU - Carlson, A.L.

AU - Heidt, T.

AU - Majmudar, M.D.

AU - Lasitschka, F.

AU - Etzrodt, M.

AU - Waterman, P.

AU - Waring, M.T.

AU - Chicoine, A.T.

AU - van der Laan, A.M.

AU - Niessen, H.W.M.

AU - Piek, J.J.

AU - Rubin, B.B.

AU - Butany, J.

AU - Stone, J.R.

AU - Katus, H.A.

AU - Murphy, S.A.

AU - Morrow, D.A.

AU - Sabatine, M.S.

AU - Vinegoni, C.

AU - Moskowitz, M.A.

AU - Pittet, M.J.

AU - Libby, P.

AU - Lin, C.P.

AU - Swirski, F.K.

AU - Weissleder, R.

AU - Nahrendorf, M.

PY - 2012/7/19

Y1 - 2012/7/19

N2 - 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.

AB - 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.

KW - Animals

KW - Apolipoproteins E

KW - Atherosclerosis

KW - Hematopoietic Stem Cells

KW - Inflammation

KW - Mice

KW - Mice, Inbred C57BL

KW - Monocytes

KW - Myocardial Infarction

KW - Spleen

KW - Stem Cells

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/nature11260

DO - 10.1038/nature11260

M3 - Article

VL - 487

SP - 325

EP - 329

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7407

ER -

Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS et al. Myocardial infarction accelerates atherosclerosis. Nature. 2012 Jul 19;487(7407):325-329. https://doi.org/10.1038/nature11260