Doctor of Philosophy (PhD)
Integrative Physiology & Molecular Medicine
Dr. Merry L. Lindsey
Cardiac remodeling after myocardial infarction (MI) is indicated by infarct wall thinning, reduced ejection fraction, and dilation of the left ventricle (LV). Inflammation presides in the early days of MI as a key event in cardiac wound healing. Infiltration of inflammatory cells, predominantly neutrophils and macrophages, is stimulated by ischemic cardiomyocytes that secrete inflammatory cues. This dissertation focused on identifying factors that influence cardiac remodeling after MI. S100A9 is a neutrophil-derived factor identified that exacerbated infarct wall thinning and cardiac dilation by increasing neutrophil and macrophage infiltration. Similarly, murinoglobulin 1 (Mug1) and galectin (Lgals)3 were macrophage-derived factors identified that regulate neutrophil degranulation and correlate with infarct wall thickness. Matrix metalloproteinase (MMP)-12 was released by both neutrophils and macrophages after MI and mapping the MMP-12 signalome revealed that MMP-12 induced neutrophil apoptosis. In my current project, I identified 5 plasma markers of adverse cardiac remodeling after MI in a retrospective study at MI D3: apolipoprotein A1 (ApoA1), interleukin (IL)17E, immunoglobulin (Ig)A, haptoglobin, and tissue inhibitor of matrix metalloproteinases (TIMP)-1. ApoA1, IL-17E, IgA, and TIMP1 in the plasma mirrored cardiac dysfunction after MI in a prospective study at MI D7. In conclusion, this thesis identified prominent modulators that influenced cardiac remodeling after MI.
Chalise, Upendra, "Modulating Cardiac Remodeling After Myocardial Infarction" (2022). Theses & Dissertations. 614.