Partha Dutta 1 , Gabriel Courties 1 , Ying Wei 2 , Florian Leuschner 1 , 3 , Rostic Gorbatov 1 , Clinton Robbins 1 , Yoshiko Iwamoto 1 , Brian Thompson 1 , Alicia L. Carlson 1 , Timo Heidt 1 , Maulik D. Majmudar 1 , 4 , Felix Lasitschka 5 , Martin Etzrodt 1 , Peter Waterman 1 , Michael T. Waring 6 , 7 , Adam T. Chicoine 6 , 7 , Anja M. van der Laan 8 , Hans W.M. Niessen 9 , Jan J. Piek 8 , Barry B. Rubin 10 , Jagdish Butany 11 , James Stone 1 , Hugo A. Katus 3 , Sabina A. Murphy 12 , David A. Morrow 12 , Marc S. Sabatine 12 , Claudio Vinegoni 1 , Michael A. Moskowitz 2 , Mikael J. Pittet 1 , Peter Libby 4 , Charles P. Lin 1 , Filip K. Swirski 1 , Ralph Weissleder 1 , 13 , Matthias Nahrendorf 1
19 January 2013
During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaque in the arterial wall and cause its 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 ischemic 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. When seeking the source of surplus monocytes in plaque, we found that myocardial infarction liberated hematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signaling. 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.