Monocytes in myocardial infarction

Abstract

Myocardial infarction (MI) is the leading cause of death in developed countries. Though timely revascularization of the ischemic myocardium and current standard therapy reduce acute mortality after MI, long-term morbidity and mortality remain high. During the first 1 to 2 weeks after MI, tissues in the infarcted myocardium undergo rapid turnover, including digestion of extracellular matrix and fibrosis. Post-MI repair is crucial to survival. Monocytes recruited to the infarcted myocardium remove debris and facilitate the repair process. However, exaggerated inflammation may also impede healing, as demonstrated by the association between elevated white blood cell count and in-hospital mortality after MI. Monocytes produced in the bone marrow and spleen enter the blood after MI and are recruited to the injured myocardium in 2 phases. The first phase is dominated by Ly-6c(high) monocytes and the second phase by Ly-6c(low) monocytes. Yet the number of Ly6C(low) monocytes recruited to the infarct is much lower, and Ly6C(high) monocytes can differentiate to Ly6C(low) macrophages in later healing stages. Understanding the signals regulating monocytosis after MI will help design new therapies to facilitate cardiac healing and limit heart failure.

Keywords: hematopoiesis; macrophages; monocytes; myocardial infarction.

Figure 1. Monocytosis after myocardial infarction

Myocardial infarction activates sympathetic activity in the bone marrow. Consequently, HSC niche cells, such as mesenchymal stem cells (MSC) and endothelial cells, produce lower levels of HSC retention factors, like CXCL12. This leads to increased myeloid progenitor proliferation and differentiation into monocytes. Newly made monocytes are released from the bone marrow and spleen and then recruited to the infarct via blood.