【Background】
Runx2 is a critical regulator of osteoblast differentiation; however, the pathophysiological significance of Runx2 in cardiac homeostasis remains to be elucidated.
【Methods and Results】
Murine myocardial infarction (MI) was generated by ligating the left coronary artery. Quantitative RT-PCR and immunoblot analyses revealed the up-regulation of Runx2 mRNA and protein in post-infarct myocardium. Immunofluorescent staining and flow cytometric analyses 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 exposed to MI. MI induced severe heart failure and lung congestion in CKO mice. CKO mice showed exacerbated cardiac fibrosis and function, respectively after MI. RNA sequence analyses demonstrated that myeloid expression of Runx2 regulated the gene expression responsible for vascular functions. Consistently, capillary density was decreased in CKO mice, proposing the importance of Runx2-expressing myeloid cells in cardiac repair. Single-cell RNA sequence analyses showed that Runx2-expressing cells did not coincide with either M1 and M2 macrophages.
【Conclusion】
Runx2-expressing myeloid cells prevented post-infarct cardiac remodeling as a novel cell population.