Sebastian Cremer1, Maximilian J Schloss1, Claudio Vinegoni1, Brody H Foy2, Shuang Zhang1, David Rohde1, Maarten Hulsmans1, Paolo Fumene Feruglio3, Stephen Schmidt1, Greg Wojtkiewicz1, John M Higgins2, Ralph Weissleder1, Filip K Swirski1, Matthias Nahrendorf4. 1. Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts. 2. Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts. 3. Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. 4. Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany. Electronic address: mnahrendorf@mgh.harvard.edu.
Abstract
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.
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.
Authors: Merry L Lindsey; Keith R Brunt; Jonathan A Kirk; Petra Kleinbongard; John W Calvert; Lisandra E de Castro Brás; Kristine Y DeLeon-Pennell; Dominic P Del Re; Nikolaos G Frangogiannis; Stefan Frantz; Richard J Gumina; Ganesh V Halade; Steven P Jones; Rebecca H Ritchie; Francis G Spinale; Edward B Thorp; Crystal M Ripplinger; Zamaneh Kassiri Journal: Am J Physiol Heart Circ Physiol Date: 2021-10-08 Impact factor: 5.125
Authors: Merry L Lindsey; Lisandra E de Castro Brás; Kristine Y DeLeon-Pennell; Nikolaos G Frangogiannis; Ganesh V Halade; Caitlin C O'Meara; Francis G Spinale; Zamaneh Kassiri; Jonathan A Kirk; Petra Kleinbongard; Crystal M Ripplinger; Keith R Brunt Journal: Am J Physiol Heart Circ Physiol Date: 2021-06-11 Impact factor: 5.125
Authors: Wolf-Stephan Rudi; Michael Molitor; Venkata Garlapati; Stefanie Finger; Johannes Wild; Thomas Münzel; Susanne H Karbach; Philip Wenzel Journal: Antioxidants (Basel) Date: 2021-03-05
Authors: Rudolf A de Boer; Joseph Pierre Aboumsallem; Valentina Bracun; Douglas Leedy; Richard Cheng; Sahishnu Patel; David Rayan; Svetlana Zaharova; Jennifer Rymer; Jennifer M Kwan; Joshua Levenson; Claudio Ronco; Paaladinesh Thavendiranathan; Sherry-Ann Brown Journal: Cardiooncology Date: 2021-06-21