About one in four myocardial infarction (MI) patients progress to develop congestive heart failure, which has a 5-year mortality rate of 50%. The goal of this project is to understand post-MI roles of neutrophils by establishing how this cell type transitions in phenotype during wound healing spanning from inflammation to repair. We hypothesize that neutrophils undergo a temporal phenotype evolution that includes influencing post-MI inflammation resolution and ECM organization.
Specific aim 1 will map neutrophil polarization phenotypes over the post-MI time course.
Aim 2 will test the hypothesis that neutrophils actively contribute to inflammation resolution.
Aim 3 will test the hypothesis that neutrophils actively contribute to extracellular matrix organization during scar formation. Innovation lies in the evaluation of neutrophil subtypes post-MI, which will allow us to connect early neutrophil cell physiology to late remodeling outcomes. Multi-discipline approaches will be integrated to explore the mechanisms whereby neutrophils regulate remodeling. This study will drive forward the understanding of the cellular basis of LV remodeling and identify novel intervention targets directed at neutrophils.
Heart failure is the inability of the heart to pump adequately to supply the body with sufficient oxygen to meet its needs, and heart failure is a leading cause of death in the United States, the veteran population included. Of the 50,000 individuals diagnosed with heart failure each year, 70% of these patients have heart failure due to a previous heart attack (myocardial infarction; MI). The main objective of this grant is to use a mouse MI model to understand how one of the white blood cell types, the neutrophil, influences scar formation by regulating the wound healing response, particularly the inflammatory and reparative components.
| Lindsey, Merry L; Bolli, Roberto; Canty Jr, John M et al. (2018) Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol 314:H812-H838 |
| Ma, Yonggang; Mouton, Alan J; Lindsey, Merry L (2018) Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction. Transl Res 191:15-28 |
| Lindsey, Merry L; Gray, Gillian A; Wood, Susan K et al. (2018) Statistical considerations in reporting cardiovascular research. Am J Physiol Heart Circ Physiol 315:H303-H313 |
| Mouton, Alan J; DeLeon-Pennell, Kristine Y; Rivera Gonzalez, Osvaldo J et al. (2018) Mapping macrophage polarization over the myocardial infarction time continuum. Basic Res Cardiol 113:26 |
| Lindsey, Merry L; Jung, Mira; Yabluchanskiy, Andriy et al. (2018) Exogenous CXCL4 Infusion Inhibits Macrophage Phagocytosis by Limiting CD36 Signaling to Enhance Post-myocardial Infarction Cardiac Dilation and Mortality. Cardiovasc Res : |
| Lindsey, Merry L (2018) Reg-ulating macrophage infiltration to alter wound healing following myocardial infarction. Cardiovasc Res 114:1571-1572 |
| DeLeon-Pennell, Kristine Y; Mouton, Alan J; Ero, Osasere K et al. (2018) LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling. Basic Res Cardiol 113:40 |
| Lindsey, Merry L; Kassiri, Zamaneh; Virag, Jitka A I et al. (2018) Guidelines for measuring cardiac physiology in mice. Am J Physiol Heart Circ Physiol 314:H733-H752 |
| Lindsey, Merry L; Jung, Mira; Hall, Michael E et al. (2018) Proteomic analysis of the cardiac extracellular matrix: clinical research applications. Expert Rev Proteomics 15:105-112 |
| Mouton, Alan J; Rivera Gonzalez, Osvaldo J; Kaminski, Amanda R et al. (2018) Matrix metalloproteinase-12 as an endogenous resolution promoting factor following myocardial infarction. Pharmacol Res 137:252-258 |
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