Role of macrophage migration inhibition factor (MIF) in induced cardiac hypertrophy, The

Pacheco, Benjamin
Cardiovascular disease is the leading killer in industrialized nations. Currently, there are 5 million Americans experiencing chronic heart failure with a 5-year survival rate of less than 50%. This poses a serious challenge for healthcare professionals and researchers alike, as the frequency of cardiovascular disease cases continues to increase. Hypertrophy is the primary mechanism through which the heart undergoes reconstruction to cope with increased ventricular workload. This process is characterized by an increase in protein synthesis and enlargement of cardiomyocytes. Pathological cardiac hypertrophy often results in irreversible heart dysfunction. Currently, the mechanisms behind hypertrophy-associated heart failure are not fully known. Autophagy is an essential means of clearing the cell of older organelles and proteins. Recently, accumulating evidence has surfaced in support of the important role of autophagy in the heart. Under physiological conditions, autophagy is cytoprotective by recycling long-lived proteins and organelles, and generating new macromolecules. On the other hand, pathological autophagy can be detrimental to the cell because of excessive degradation of cytoplasmic constituents. For years, autophagy has been implicated in the development of heart hypertrophy. Induced pressure overload by transverse aortic constriction (TAC) induces hypertrophy one week after surgery, leading to decreased autophagic activity. Recent studies suggest that decreased autophagy may facilitate cardiac hypertrophy progress. However, the mechanism connecting hypertrophy and autophagy is still elusive. Modern evidence indicates AMPK to be an upstream mediator of autophagic flux. AMPK is also reported to safeguard the heart against hypertrophy, through phosphorylation by various factors. Current research also supports the notion of macrophage migration inhibition factor (MIF), a proinflammatory cytokine released from immune cells, as being a strong inducer of AMPK phosphorylation, thus protecting the heart against ischemia and restoring reperfusion. However, there is no current research that explores the role of MIF in the development of cardiac hypertrophy induced by chronic pressure overload. Therefore, this proposed study will focus on understanding the role of MIF in the development of cardiac hypertrophy in response to chronic work overload. My central hypothesis is by mediating the autophagic flux, MIF can protect murine cardiomyocytes in response to chronic pressure overload.
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