Journal Article

Myocardial infarction accelerates atherosclerosis

Heidt, Timo, van der Laan, Anja M., Swirski, Filip K., Lin, Charles P., Gorbatov, Rostic, Dutta, Partha, Wei, Ying, Piek, Jan J., Courties, Gabriel, Carlson, Alicia L., Nahrendorf, Matthias, Thompson, Brian, Sabatine, Marc S., Leuschner, Florian, Stone, James R., Pittet, Mikael J., Etzrodt, Martin, Murphy, Sabina A., Robbins, Clinton S., Butany, Jagdish, Rubin, Barry B., Moskowitz, Michael A., Weissleder, Ralph, Niessen, Hans W. M., Libby, Peter, Lasitschka, Felix, Iwamoto, Yoshiko, Waring, Michael T., Waterman, Peter, Majmudar, Maulik D., Chicoine, Adam T., Morrow, David A., Katus, Hugo A., Vinegoni, Claudio

2012

Overview

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. Myocardial infarction accelerates atherosclerosis through activation of the sympathetic nervous system, and the consequent release of haematopoietic stem and progenitor cells. Recurrent heart attack risk Patients who have a myocardial infarction are at high risk of recurrent events. This study shows for the first time that myocardial infarction and stroke accelerate atherosclerosis. The authors were able to demonstrate that myocardial infarction leads to activation of the sympathetic nervous system, which, in turn, leads to the release of haematopoietic stem cells and progenitor cells. These cells seeded in the spleen and augmented the production of monocytes displaying an enhanced atherogenic phenotype. These findings were correlated with patient data showing that prior beta-blocker therapy was associated with a decrease in circulating monocytes after myocardial infarction. These findings suggest that interventions that interrupt the supply of monocytes could attenuate atherosclerosis and may improve long-term patient outcomes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/249/2510/2100 / 631/532 / 692/420/2780 / 692/699/75/2/1674 / Analysis / Animals / Apolipoproteins E - genetics / Atherosclerosis / Atherosclerosis (general aspects, experimental research) / Atherosclerosis - etiology / Atherosclerosis - pathology / Biological and medical sciences / Blood and lymphatic vessels / Bone marrow / Cardiology. Vascular system / Cell adhesion & migration / Complications and side effects / Coronary heart disease / Development and progression / Evaluation / Health aspects / Heart / Heart attack / Hematopoietic stem cells / Hematopoietic Stem Cells - cytology / Humanities and Social Sciences / Hypotheses / Inflammation - complications / Medical sciences / Mice / Mice, Inbred C57BL / Monocytes - cytology / multidisciplinary / Myocardial infarction / Myocardial Infarction - complications / Myocardial Infarction - pathology / Prognosis / Proteases / Proteins / Risk factors / Rodents / Science / Spleen / Spleen - cytology / Stem cells / Stem Cells - cytology / Stroke / Studies / Tomography