Diminished Reactive Hematopoiesis and Cardiac Inflammation in a Mouse Model of Recurrent Myocardial Infarction

J Am Coll Cardiol. 2020 Mar 3;75(8):901-915. doi: 10.1016/j.jacc.2019.12.056.


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.

Keywords: bone marrow; emergency hematopoiesis; immune memory; inflammation; recurrent myocardial infarction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Anterior Wall Myocardial Infarction / blood
  • Anterior Wall Myocardial Infarction / immunology*
  • Disease Models, Animal*
  • Female
  • Hematopoiesis*
  • Humans
  • Leukocytosis
  • Macrophages / physiology
  • Male
  • Mice
  • Middle Aged
  • Parabiosis
  • Recurrence
  • Retrospective Studies