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.
authors: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors: Partha
authors: P
authors: Dutta
authors: Gabriel
authors: G
authors: Courties
authors: Ying
authors: Y
authors: Wei
authors: Florian
authors: F
authors: Leuschner
authors: Rostic
authors: R
authors: Gorbatov
authors: Clinton S
authors: CS
authors: Robbins
authors: Yoshiko
authors: Y
authors: Iwamoto
authors: Brian
authors: B
authors: Thompson
authors: Alicia L
authors: AL
authors: Carlson
authors: Timo
authors: T
authors: Heidt
authors: Maulik D
authors: MD
authors: Majmudar
authors: Felix
authors: F
authors: Lasitschka
authors: Martin
authors: M
authors: Etzrodt
authors: Peter
authors: P
authors: Waterman
authors: Michael T
authors: MT
authors: Waring
authors: Adam T
authors: AT
authors: Chicoine
authors: Anja M
authors: AM
authors: van der Laan
authors: Hans W M
authors: HW
authors: Niessen
authors: Jan J
authors: JJ
authors: Piek
authors: Barry B
authors: BB
authors: Rubin
authors: Jagdish
authors: J
authors: Butany
authors: James R
authors: JR
authors: Stone
authors: Hugo A
authors: HA
authors: Katus
authors: Sabina A
authors: SA
authors: Murphy
authors: David A
authors: DA
authors: Morrow
authors: Marc S
authors: MS
authors: Sabatine
authors: Claudio
authors: C
authors: Vinegoni
authors: Michael A
authors: MA
authors: Moskowitz
authors: Mikael J
authors: MJ
authors: Pittet
authors: Peter
authors: P
authors: Libby
authors: Charles P
authors: CP
authors: Lin
authors: Filip K
authors: FK
authors: Swirski
authors: Ralph
authors: R
authors: Weissleder
authors: Matthias
authors: M
authors: Nahrendorf
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007249:Inflammation / Q000150:complications; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology*; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology
chemical_list: D001057:Apolipoproteins E