Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction
Autor: | Gregory R. Wojtkiewicz, Sebastian Cremer, Maximilian J. Schloss, Ralph Weissleder, Matthias Nahrendorf, Stephen D. Schmidt, Paolo Fumene Feruglio, Brody H. Foy, Filip K. Swirski, Shuang Zhang, Maarten Hulsmans, Claudio Vinegoni, David Rohde, John M. Higgins |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Myeloid bone marrow Leukocytosis Ischemia Parabiosis Inflammation 030204 cardiovascular system & hematology Anterior Descending Coronary Artery emergency hematopoiesis immune memory inflammation recurrent myocardial infarction Coronary artery disease Mice 03 medical and health sciences 0302 clinical medicine Recurrence Internal medicine medicine Animals Humans 030212 general & internal medicine Anterior Wall Myocardial Infarction Aged Retrospective Studies Aged 80 and over biology business.industry Macrophages Middle Aged medicine.disease Troponin Hematopoiesis Disease Models Animal medicine.anatomical_structure Cardiology biology.protein Female Bone marrow medicine.symptom Cardiology and Cardiovascular Medicine business |
Popis: | Background Recurrent myocardial infarction (MI) is common in patients with coronary artery disease and is associated with high mortality. Long-term reprogramming of myeloid progenitors occurs in response to inflammatory stimuli and alters the organism’s response to secondary inflammatory challenges. Objectives This study examined the effect of recurrent MI on bone marrow response and cardiac inflammation. Methods The investigators developed a surgical mouse model in which 2 subsequent MIs affected different left ventricular regions in the same mouse. Recurrent MI was induced by ligating the left circumflex artery followed by the left anterior descending coronary artery branch. The study characterized the resulting ischemia by whole-heart fluorescent coronary angiography after optical organ clearing and by cardiac magnetic resonance imaging. Results A first MI-induced bone marrow “memory” via a circulating signal, reducing hematopoietic maintenance factor expression in bone marrow macrophages. This dampened the organism’s reaction to subsequent events. Despite a similar extent of injury according to troponin levels, recurrent MI caused reduced emergency hematopoiesis and less leukocytosis than a first MI. Consequently, fewer leukocytes migrated to the ischemic myocardium. The hematopoietic response to lipopolysaccharide was also mitigated after a previous MI. The increase of white blood count in 28 patients was lower after recurrent MI compared with their first MI. Conclusions The data suggested that hematopoietic and innate immune responses are shaped by a preceding MI. |
Databáze: | OpenAIRE |
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