Macrophage activation and polarization in post-infarction cardiac remodeling

Abstract

Adverse cardiac remodeling leads to impaired ventricular function and heart failure, remaining a major cause of mortality and morbidity in patients with acute myocardial infarction. It have been shown that, even if all the recommended therapies for ST-segment elevation myocardial infarction are performed, one third of patients undergoes progressive cardiac remodeling that represents morphological basis for following heart failure. The need to extend our knowledge about factors leading to different clinical scenarios of myocardial infarction and following complications has resulted in a research of immuno-inflammatory pathways and molecular activities as the basis for post-infarction remodeling. Recently, macrophages (cells of the innate immune system) have become a subject of scientific interest under both normal and pathological conditions. Macrophages, besides their role in host protection and tissue homeostasis, play an important role in pathophysiological processes induced by myocardial infarction. In this article we summarize data about the function of monocytes and macrophages plasticity in myocardial infarction and outline potential role of these cells as effective targets to control processes of inflammation, cardiac remodeling and healing following acute coronary event.

Keywords: Heart failure; Inflammation; Macrophages; Monocytes; Myocardial infarction; Remodeling.

Fig. 1

a Paradigms dealing with mechanisms of cardiac remodeling after myocardial infarction. In the early phase of injury, ventricular remodeling is an effect of infarct expansion; in late phase it involves reactive myocyte hypertrophy, interstitial fibrosis and left ventricular dilatation. Changes of the extracellular collagen matrix in infarct heart play an important role in cardiac remodeling A huge number of endogenous factors affect the extracellular collagen matrix in different ways, causing degradation or synthesis of its components. b Cardiomyocyte necrosis triggers an activation of innate immune system and a cascade of inflammatory pathways. In response to ischemic injury monocytes are recruited from the bone marrow and spleen to the heart and become monocyte-derived macrophages. Macrophages produce pro- and anti-inflammatory factors, promote resorption of cellular debris, regulation of granulation tissue formation and neoangiogenesis. The search of therapeutic target, which is able to prevent, limit or reverse adverse cardiac remodelingg is one of the most important and complicated tasks of modern cardiology