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Cellular & Integrative Physiology
Merry L. Lindsey, Ph.D.
Merry L. Lindsey, Ph.D.
Myocardial Infarction (MI) results in a loss of cardiomyocytes, which stimulates a wound healing response to form scar tissue in the heart. Mapping inflammatory and extracellular matrix (ECM) gene changes after MI will help us to understand the temporal evolution in profiles. Using the Mouse Heart Attack Research Tool (mHART), a comprehensive database of previous MI studies in wild-type C57/BL6J mice, we retrospectively analyzed gene array data that included 84 inflammatory genes (n=91 mice) and 84 ECM genes (n=109 mice) at time 0 (no MI) and MI day (D)1, 3, 5, 7, and 28. Temporal evolution was assessed by ANOVA, and unpaired t-test was used to compare consecutive days. Ingenuity Pathway Analysis was used for data visualization and to identify pathways enriched at specific MI days. Overall, we saw three major shifts in wound healing after MI. The first was an early robust inflammation at D1 and D3, shifting to resolution of inflammation by D5 and D7, and leading to establishment of a neo-homeostasis by MI D28. The major genes represented at MI D1 were IL1b, IL1a, and IFNg; at D3 were inhibition of IL13, IL4, and C3; at D5 were activation of TGFb1, IFNg, and TNF; at D7 were inhibition of TNF, IL17Ra and IL36A; and at D28 inhibition of IFNg, CCR5, and CCR2. The transition from D0 to MI D1 showed maximum activation of the inflammatory response, with the primary pathways induced being activation and adhesion of neutrophils, cellular movement, and recruitment of antigen presenting cells. The signaling pathways induced during the shift from MI D5 to D7 included inhibition of cellular infiltration of myeloid cells and inhibition of chemotaxis of monocytes. Pathways induced from MI D7 to D28 indicated a shift to the new homeostasis indicated by further inhibition of cellular movement and inhibition of growth of blood vessels. In summary, our evaluation revealed a steady shift in signaling from early inflammation to resolution and repair over the course of MI.
Myocardial Infarction, Gene Array, Extracellular Matrix, Inflammatory, mouse Heart Attack Tool (mHART)
Abdool, Aisha Y.; Lindsey, Merry L.; and Chalise, Upendra, "Using Big Data Approaches to Map Myocardial Infarction Signatures" (2021). Posters: 2021 Summer Undergraduate Research Program. 4.