Development of therapeutic systems to treat the infarcted heart
Gray, Warren Dale
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Cardiovascular disease is the leading cause of morbidity and mortality in developed nations, and heart disease is predicted to remain the leading killer for the foreseeable future. Acute myocardial infarctions—nearly 1.1 million annually occurring in the U.S. alone—are the major cardiovascular disease subgroup. Current treatments for myocardial infarction are limited to interventions that serve to mitigate the initial insult, but clinical applications to protect or regenerate damaged myocardium are lacking. This dissertation examines three therapeutic systems to treat the infarcted heart. First, the decoration of a polymeric nanoparticle with N-acetylglucosamine for the uptake of anti-apoptotic therapeutics to ameliorate cardiomyocyte cell death. Second, novel dendrimeric structure architecture to allow for regioselected decoration of ligands to induce angiogenesis. Third, exosomes secreted from hypoxic cardiac progenitor cells as a naturally derived therapeuticfor angiogenesis and anti-fibrosis, and to provide bio-inspired clues for future therapies.