Abstract 17755: Cardiac Myosin Binding Protein C Contributes to the Protection of the Heart During Immune Response to Infection Academic Article uri icon


  • Infections can exacerbate heart failure and contribute to heart transplant rejection. We hypothesize that cardiac myosin binding protein C (MyBPC3), a thick filament protein, contributes to protection of the heart during an immune response to infection. We tested our hypothesis by comparing wild type (WT) vs. MyBPC3(-/-) mice for their immunologic response to non-pathogenic doses of Eschericia coli lipopolysaccharide (LPS). LPS caused increased hypertrophy, worsening of diastolic dysfunction, and increased apoptosis in MyBP3(-/-) hearts. We then performed flow cytometric analyses on immune cells isolated from the myocardium, the spleen, and the bone marrow. Prior to LPS challenge, MyBPC3(-/-) hearts have relatively fewer myeloid cells characterized by CD11b+GR1High in comparison to WT hearts. LPS challenge dramatically increased myeloid cell population in WT, but not in MyBPC3(-/-) hearts. Thus, myeloid population demonstrated inverse relationship with cardiac dysfunction and apoptosis. LPS increased B cells(CD19+) infiltration into MyBPC3(-/-) hearts only, suggesting that increases in B cells correlate with increased cardiac myocyte cell death. In spleen, LPS increased total number of immune cells of all types (CD45+) only in WT. MyBPC3(-/-) showed depressed myeloid cell populations in spleen and bone marrow. Thus, loss of MyBPC3 may have contributed to overall decreased myeloid population. These results suggest that CD11b+GR1High cells are myeloid derived suppressor cells (MDSC) which protect cardiac myocytes during an immune response, and B cells are associated with cardiac myocyte cell death. Furthermore, MyBPC3 may be necessary to recruit MDSCs to maintain protection of the heart during infection. Finally, these results imply that modulating recruitment of MDSCs and preservation of MyBPC3 may provide the basis for new treatments to prevent infection-associated exacerbation of heart failure and heart transplant rejection.

published proceedings

  • Circulation

author list (cited authors)

  • Dusio, G., Liu, Y., Tobin, R. P., Mukherjee, S., Mukhopadhyay, D., Rosas, P. C., Newell Rogers, M. K., & Tong, C. W.

citation count

  • 0

complete list of authors

  • Dusio, Giuseppina||Liu, Yang||Tobin, Richard P||Mukherjee, Sanjib||Mukhopadhyay, Dhriti||Rosas, Paola C||Newell Rogers, Martha K||Tong, Carl W

publication date

  • November 2014