Macrophages in the Inflammatory Phase following Myocardial Infarction: Role of Exogenous Ubiquitin

SIMPLE SUMMARY: Heart disease is a major cause of death worldwide. A common implication of heart disease is myocardial infarction, commonly known as heart attack. Generally, myocardial infarction happens when the blood supply to a portion of the heart is reduced or blocked due to fat buildup. This blockage of blood flow damages part of the heart muscle and decreases heart function. To compensate for this injury, the heart initiates remodeling which consists of three overlapping phases of inflammation, proliferation, and maturation. This review focusses on the inflammatory phase, specifically the roles of macrophages and ubiquitin in heart repair following myocardial infarction, and discusses how ubiquitin could impact macrophage function. Macrophages are specialized blood cells with a critical role in wound healing. Ubiquitin is a highly evolutionarily conserved protein found in plasma. Plasma ubiquitin levels are increased in several disease states, including heart disease. ABSTRACT: Cardiovascular disease (CVD) is one of the leading causes of death worldwide. One of the most common implications of CVD is myocardial infarction (MI). Following MI, the repair of the infarcted heart occurs through three distinct, yet overlapping phases of inflammation, proliferation, and maturation. Macrophages are essential to the resolution of the inflammatory phase due to their role in phagocytosis and efferocytosis. However, excessive and long-term macrophage accumulation at the area of injury and dysregulated function can induce adverse cardiac remodeling post-MI. Ubiquitin (UB) is a highly evolutionarily conserved small protein and is a normal constituent of plasma. Levels of UB are increased in the plasma during a variety of pathological conditions, including ischemic heart disease. Treatment of mice with UB associates with decreased inflammatory response and improved heart function following ischemia/reperfusion injury. This review summarizes the role of macrophages in the infarct healing process of the heart post-MI, and discusses the role of exogenous UB in myocardial remodeling post-MI and in the modulation of macrophage phenotype and function.