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Research in the Fan lab has three main areas

Myocardial ischemia/reperfusion (I/R) injury and repair

Reperfusion of ischemic hearts by percutaneous coronary intervention, cardiac surgery or thrombolytic therapy is commonly used in patients with myocardial infarction. However, it is well-recognized that reperfusion could induce excessive oxidative stress and inflammation, leading to myocyte death (apoptosis and necrosis). Over the past two decades, we have made a great contribution to understand the mechanisms associated with myocardial I/R injury and repair.  We demonstrated that Hsp20 overexpression in transgenic mice is cardioprotective against I/R injury (Circulation, 2005) and Hsp20 opposes beta-adrenergic agonist-induced cardiomyocyte apoptosis during ventricular remodeling (Circ. Res. 2006). Importantly, we went on to show that the mechanism of Hsp20-induced protection involves Akt activation (Circ. Res. 2008). Later, our research team discovered that miRNA-320 is detrimental during cardiac I/R, whereas miR-494 is protective against I/R-induced cardiac damage (Circulation, 2009 & 2010). We also reported that miR-223 is involved in exercise-induced physiological cardiac hypertrophy and both strands of miR-223 could provide cardio-protection against I/R-triggered myocyte necroptosis (J. Biol. Chem. 2016 a/b).

Recently, we are moving forward to elucidate how macrophages regulate myocardial I/R injury and repair through polarization and efferocytosis.

Sepsis and its associated vascular leakage and cardiac dysfunction

Sepsis is characterized as life-threatening multi-organ dysfunction caused by a dysregulated host response to infection. Although aggressive antibiotic treatments are applied to control bacterial infection at the early stage, sepsis remains a leading cause of death in intensive care units. Specifically, cardiac dysfunction has been linked with increased risk of mortality and morbidity in septic patients.  Over the past decade, we have defined the role of exosomes and miRNAs in sepsis-triggered vascular leakage and cardiac dysfunction (Biochim Biophys Acta, 2014 a/b, 2015; Sci. Rep. 2015; J Infect Dis. 2016; Shock, 2016 & 2018; J Biol Chem. 2019).

Recently, our focus is moving forward to determine the role of bacteria-released membrane vesicles and some novel proteins (i.e., Sectm1a, Lcn10) in the regulation of macrophage function (polarization and phagocytosis) and endothelial permebility as well as cardiac function.

Diabetes-induced cardiomyopathy

Diabetes mellitus (DM) is a chronic endocrine and metabolic disorder characterized by hyperglycemia due to defective insulin secretion, action, peripheral insulin resistance or all of them. Notably, patients with diabetes are at two to three folds higher risk of developing cardiovascular disease. Interestingly, using diabetic animal models, we identified a novel mechanism underlying diabetes mellitus-induced myocardial vascular deficiency which may be caused by secretion of anti-angiogenic exosomes from cardiomyocytes (J Mol Cell Cardiol. 2014). We further discovered that Hsp20-modified cardiomyocytes can offer protection in diabetic hearts through the release of instrumental exosomes (Diabetes, 2016).  Currently, we are focusing on macrophage polarization in diabetic hearts (Cardiovasc Res. 2021).

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Department of
Pharmacology and Systems Physiology

College of Medicine
231 Albert Sabin Way
Cincinnati, OH 45267-0575

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