Abstract 14819: Myeloid Cell-Specific Runx2 Deficiency Exacerbates Adverse Cardiac Remodeling After Myocardial Infarction
Background and Objective: Runx2 was originally identified as a transcriptional factor that is responsible for osteoblast differentiation. Accumulating evidence has reported that Runx2 plays important roles in pathogenesis of cardiovascular diseases, especially in vascular calcification; however, pathophysiological significance of Runx2 in heart failure remains to be elucidated.
Methods and Results: Myocardial infarction (MI) was generated in C57Bl/6 mice by ligation of left coronary artery. The expression of Runx2 transcript and protein was upregulated after MI, analyzed by real time PCR and western blotting. Immunofluorescent microscopy demonstrated that Runx2 was expressed in CD11b+ cells. Flow cytometry analyses also showed that Runx2 was expressed in heart-infiltrating CD11b+ myeloid cells after MI. To analyze the biological functions of Runx2 during post-infarct cardiac remodeling, myeloid cell-specific Runx2 deficient mice (CKO mice) were generated by breeding LysM-Cre mice with the Runx2 flox mice and exposed to MI. Fourteen days after MI, both ventricular/tibia ratio and lung/tibia ratio were increased in CKO mice (ventricular; Runx2 flox: 6.0±0.6, CKO: 6.9±0.4, lung; Runx2 flox: 6.8±1.4, CKO: 8.2±1.1, P<0.05, N=11 for Runx2 flox, N=13 for CKO). Echocardiography showed that %FS and LVEF were reduced in KO mice after MI, compared with Runx2 flox mice (FS; Runx2 flox:34.7±4.5, CKO:29.0±2.8, LVEF; Runx2 flox: 71.8±5.9, CKO: 64.0±3.9, P<0.05, N=5 for Runx2 flox, N=6 for CKO). Masson’s trichrome staining revealed that cardiac fibrosis exacerbated in KO mice (Runx2 flox: 37.0±8.5, CKO: 49.7±7.1, P<0.05, N=11 for Runx2 flox, N=13 for CKO). Immunohistochemical analyzes using anti-CD31 antibody showed that capillary density was decreased at border zone of the hearts after MI in CKO mice compared with Runx2 flox mice (Runx2 flox: 2378.2±233.9, CKO: 2049.0±377.6, P<0.05, N=11 for Runx2 flox, N=13 for CKO).
Conclusion: Runx2 was expressed in heart-infiltrating myeloid cells after MI and contributed to prevent the adverse cardiac remodeling. Runx2 could be a novel therapeutic target against heart failure after MI.
Author Disclosures: M. Ashizuka: None. S. Kumagai: None. E. Yanase: None. M. Obana: None. M. Maeda: None. Y. Sakata: None. H. Nakayama: None. Y. Fujio: None.
- © 2016 by American Heart Association, Inc.