Publication Date:
2012-07-06
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401326/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401326/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dutta, Partha -- Courties, Gabriel -- Wei, Ying -- Leuschner, Florian -- Gorbatov, Rostic -- Robbins, Clinton S -- Iwamoto, Yoshiko -- Thompson, Brian -- Carlson, Alicia L -- Heidt, Timo -- Majmudar, Maulik D -- Lasitschka, Felix -- Etzrodt, Martin -- Waterman, Peter -- Waring, Michael T -- Chicoine, Adam T -- van der Laan, Anja M -- Niessen, Hans W M -- Piek, Jan J -- Rubin, Barry B -- Butany, Jagdish -- Stone, James R -- Katus, Hugo A -- Murphy, Sabina A -- Morrow, David A -- Sabatine, Marc S -- Vinegoni, Claudio -- Moskowitz, Michael A -- Pittet, Mikael J -- Libby, Peter -- Lin, Charles P -- Swirski, Filip K -- Weissleder, Ralph -- Nahrendorf, Matthias -- P50-CA086355/CA/NCI NIH HHS/ -- R01 AI084880/AI/NIAID NIH HHS/ -- R01 EB006432/EB/NIBIB NIH HHS/ -- R01 HL095612/HL/NHLBI NIH HHS/ -- R01 HL095629/HL/NHLBI NIH HHS/ -- R01 HL096576/HL/NHLBI NIH HHS/ -- R01-EB006432/EB/NIBIB NIH HHS/ -- R01-HL095629/HL/NHLBI NIH HHS/ -- R01-HL096576/HL/NHLBI NIH HHS/ -- T32 CA079443/CA/NCI NIH HHS/ -- T32-CA79443/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jul 19;487(7407):325-9. doi: 10.1038/nature11260.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22763456" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Apolipoproteins E/genetics
;
Atherosclerosis/*etiology/*pathology
;
Hematopoietic Stem Cells/cytology
;
Inflammation/complications
;
Mice
;
Mice, Inbred C57BL
;
Monocytes/cytology
;
Myocardial Infarction/*complications/*pathology
;
Spleen/cytology
;
Stem Cells/cytology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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