Monocytes: protagonists of infarct inflammation and repair after myocardial infarction

M Nahrendorf, MJ Pittet, FK Swirski - Circulation, 2010 - Am Heart Assoc
Circulation, 2010Am Heart Assoc
Myocardial infarction (MI) is the most frequent cause of heart failure, which is an
incapacitating disease with high prevalence and broad socioeconomic impact. In 2008 in
the United States, 5.7 million people suffered from heart failure, and more than 287 000
people died. 1 Timely revascularization of ischemic myocardium reduces acute infarct
mortality, and current standard therapy with blockers and angiotensin-converting enzyme
(ACE) inhibitors curbs development of post-MI heart failure. For example, ACE inhibitor …
Myocardial infarction (MI) is the most frequent cause of heart failure, which is an incapacitating disease with high prevalence and broad socioeconomic impact. In 2008 in the United States, 5.7 million people suffered from heart failure, and more than 287 000 people died. 1 Timely revascularization of ischemic myocardium reduces acute infarct mortality, and current standard therapy with blockers and angiotensin-converting enzyme (ACE) inhibitors curbs development of post-MI heart failure. For example, ACE inhibitor treatment reduced mortality from 25% to 20% in the Survival and Ventricular Enlargement (SAVE) trial. 2 Although this is a major advance, long-term mortality remains high. The combination of reduced acute infarct mortality due to efficient acute care and insufficient options to treat infarct survivors chronically has contributed to an increased heart failure prevalence (Figure 1). 3 The need to understand and treat heart failure better has motivated clinicians and basic scientists to explore new therapeutic strategies to repair the failing heart, for instance, with stem cells. 4, 5 Augmentation of intrinsic wound healing that occurs during the first 1 to 2 weeks after MI is a prospective approach with the potential to prevent heart failure. During this period, the infarct is highly active biologically. 6–8 Delicate granulation tissue undergoes rapid turnover of cells and of structural components such as the extracellular matrix. Preexisting collagen is digested and new matrix is laid down. During these extensive changes of tissue architecture, the vulnerable wound is exposed to the mechanical stress of cycling intraventricular pressure and myocardial contraction, and the heart can undergo profound and deleterious changes in ventricular geometry and function. In the short term (days, weeks), poor healing can lead to infarct expansion and left ventricular dilatation and in some cases to infarct rupture and death. In the long term (months, years), filling pressure, wall stress, and left ventricular volume can increase and propagate adverse remodeling, leading to heart failure and a poor prognosis. 7, 9, 10 Conversely,“sufficient” healing preserves left ventricular geometry and prevents heart failure. In this review, we propose that the quality of infarct healing shortly after injury determines the fate of the patient for years to come.
Am Heart Assoc