Matthias Nahrendorf, MD, PhD, MGH Research Scholar Profile
MGH Research Scholar Matthias Nahrendorf, MD, PhD, is developing innovative new technologies for imaging the human body in vivo and is investigating the progression and causes of arteriosclerosis.
Immunity in Heart Failure
Weissman Family MGH Research Scholar 2014-2019
The Richard Moerschner Endowed MGH Research Institute
Investigator, Center for Systems Biology
Professor of Radiology, Harvard Medical School
Approximately 20% of patients who have had a heart attack will have a second within a year. Why?
In a study published in Nature, we describe the underlying mechanism that leads to secondary heart attacks in patients. We are now investigating therapeutic implications of this discovery.
Immunity in Heart Failure
Advanced heart failure has 50% mortality, and there are 6 million heart failure patients in the USA, creating a pressing medical need. Focusing on basic wound healing processes that occur within the first two weeks after ischemic injury, my research lead to the insight that early infarct healing is a key period after acute MI during which therapeutic interventions (there are none today) could change the long-term course of disease.
The healing infarct is a special wound: exposed to the high strain of blood pressure and cardiac motion, it cannot 'rest' like a broken bone in a cast. If healing derails, the infarct scar expands, the heart dilates, and a vicious cycle of remodeling results in heart failure.
My lab studies macrophages and their circulating progenitors (monocytes) in the setting of infarction. We discovered that there are 2 monocytic phases after MI. In the first 3 days, the infarct recruits inflammatory monocytes, then, the heart switches to a resolution phenotype on day 4.
If a phase is missing, wound healing is deficient (JEM 2007, >500 citations). These findings have been reproduced in humans. We further discovered a new function of the spleen (Science 2009) and hematopoiesis activation in the setting of myocardial infarction (JEM 2012).
The spleen harbors a large ready-to-deploy monocyte reservoir that is released post-MI through increased angiotensin-2 levels. Infarction triggers a transfer of stem cells from the bone marrow to the spleen, outsourcing production of inflammatory leukocytes.