Macrophage roles following myocardial infarction

Abstract

Following myocardial infarction (MI), circulating blood monocytes respond to chemotactic factors, migrate into the infarcted myocardium, and differentiate into macrophages. At the injury site, macrophages remove necrotic cardiac myocytes and apoptotic neutrophils; secrete cytokines, chemokines, and growth factors; and modulate phases of the angiogenic response. As such, the macrophage is a primary responder cell type that is involved in the regulation of post-MI wound healing at multiple levels. This review summarizes what is currently known about macrophage functions post-MI and borrows literature from other injury and inflammatory models to speculate on additional roles. Basic science and clinical avenues that remain to be explored are also discussed.

Figure 1

Ischemia of sufficient duration to induce myocardial infarction stimulates an inflammatory reaction that is characterized by infiltration of neutrophils during the first day and macrophages beginning at day 3. The influx of macrophage coordinates the wound healing response, which involves activation of both endothelial cells and cardiac fibroblasts. The coordination between inflammation and scar formation determines the fate post-MI.

Figure 2

Macrophage regulation of angiogenesis in ischemic tissue. 1) Vascular endothelial cells release monocyte chemotactic protein-1 (MCP-1) into the extracellular space. 2) MCP-1 attracts macrophages with the MCP-1 receptor, C-C chemokine receptor. 3) Activated macrophages secrete a variety of substances, including cytokines and matrix metalloproteinases (MMPs). 4) MMPs and TIMPs may function in early angiogenesis through interactions with extracellular matrix components. A) Degradation of matrix can release and activate extracellular matrix-bound growth factors and angiogenic molecules. MMPs and TIMPs also stimulate proliferation of endothelial and smooth muscle cells. B) MMP migration through matrix can create a pathway in the extracellular matrix for endothelial or precursor cells for angiogenesis.