Elucidating the inflammatory landscape of hearts with Hypertrophic Cardiomyopathy

objective:: Preliminary studies in our laboratory identify that High Intensity Interval Training (HIIT) can increase maximum oxygen consumption (VO2 max) in transgenic mice containing the Delta 160 variant in the troponin T gene, which causes Hypertrophic Cardiomyopathy. RNA sequencing and gene ontology analysis of heart tissue isolated from these mice identified an increase in differentially expressed transcripts involved in inflammatory responses as a major gene ontology altered in Delta 160 diseased male mice. This response was partially abrogated by HIIT. Little is known about the inflammatory microenvironment in HCM; thus we aimed to profile the inflammatory landscape of the HCM heart in three genetic mouse models of HCM. Hypothesis: We hypothesized mice containing genetic variants of HCM (Delta 160, R92L, or R506W) will exhibit an altered inflammatory response compared to wild type (WT) animals. Materials and Methods: Heart, spleen, and peripheral blood isolated from 38-week old male mice were extracted and T cell and macrophage (MO) populations were isolated. Immune cell populations were assessed via flow cytometry and quantified via FlowJo using the following markers: Live/Dead stain, CD45, CD3, CD4, CD8, FOXP3, CD11b, CD86, CD163, and CD206. Results: The percentage of live leukocytes exhibited a trend toward increase in the heart across all genotypes (R92L p<0.05) compared to WT controls, a trend that was not observed in spleen or blood. M1 macrophages showed a trend toward an increase in the cardiac tissue, which was also observed in the blood, but not splenic tissue. This paralleled a trend toward a decrease in M2 macrophages resident in the heart and spleen. Overall CD3 T cell populations were not increased in the heart or spleen, but CD4 T cells were decreased in R92L p<0.05 with a trend toward a decrease across all genotypes in the heart. Despite a reduction in CD4 T cells, Treg cells were increased across all genotypes in the heart. No changes in total T cell populations or T cell subsets were observed in the splenic tissue or blood. Conclusions: The inflammatory microenvironment of the heart is altered in the presence of genetic variants linked to HCM pathophysiology with the greatest trends observed in CD45+ leukocytes and macrophage subsets. Further biological replicates are needed to make definitive conclusions and statistical comparisons. Additionally, understanding how HIIT training modifies inflammatory response and disease pathology will be a key next step. We also intend to explore the sex differences in the inflammatory response in hypertrophic cardiomyopathy. Julia Rosenthal was sponsored by the APS SURF program. Dr. Day is supported by the NIH and Dr. Wagner was supported by the Brody Family Medical Trust Post-Doctoral Fellowship. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.