Protective role of ErbB3 signaling in myeloid cells during adaptation to cardiac pressure overload. (March 2021)

• Record Type: Journal Article
• Authors: Yin, Haifeng; Favreau-Lessard, Amanda J.; deKay, Joanne T.; Herrmann, Yodit R.; Robich, Michael P.; Koza, Robert A.; Prudovsky, Igor; Sawyer, Douglas B.; Ryzhov, Sergey
• Is Part Of: Journal of molecular and cellular cardiology. Volume 152(2021)
• Page Start: 1
• Page End: 16
• Publication Date: 2021-03
• Subjects: Transverse aortic constriction -- Non-ischemic cardiomyopathy -- ErbB3 -- Myeloid cells -- Insulin growth factor-1; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2020.11.009
• Languages: English
• ISSNs: 0022-2828

Abstract

Abstract: Background: Myeloid cells play an important role in a wide variety of cardiovascular disorders, including both ischemic and non-ischemic cardiomyopathies. Neuregulin-1 (NRG-1)/ErbB signaling has recently emerged as an important factor contributing to the control of inflammatory activation of myeloid cells after an ischemic injury. However, the role of ErbB signaling in myeloid cells in non-ischemic cardiomyopathy is not fully understood. This study investigated the role of ErbB3 receptors in the regulation of early adaptive response using a mouse model of transverse aortic constriction (TAC) for non-ischemic cardiomyopathy. Methods and results: TAC surgery was performed in groups of age- and sex-matched myeloid cell-specific ErbB3-deficient mice (ErbB3 MyeKO ) and control animals (ErbB3 MyeWT ). The number of cardiac CD45 immune cells, CD11b myeloid cells, Ly6G neutrophils, and Ly6C monocytes was determined using flow cytometric analysis. Five days after TAC, survival was dramatically reduced in male but not female ErbB3 MyeKO mice or control animals. The examination of lung weight to body weight ratio suggested that acute pulmonary edema was present in ErbB3 MyeKO male mice after TAC. To determine the cellular and molecular mechanisms involved in the increased mortality in ErbB3 MyeKO male mice, cardiac cell populations were examined at day 3 post-TAC using flow cytometry. Myeloid cells accumulated in control but not in ErbB3 MyeKO male mouse hearts. This was accompanied by increased proliferation of Sca-1 positive non-immune cells (endothelial cells and fibroblasts) in control but not ErbB3 MyeKO male mice. No significant differences in intramyocardial accumulation of myeloid cells or proliferation of Sca-1 cells were found between the groups of ErbB3 MyeKO and ErbB3 MyeWT female mice. An antibody-based protein array analysis revealed that IGF-1 expression was significantly downregulated only in ErbB3 MyeKO mice hearts compared to control animals after TAC. Conclusion: Our data demonstrate the crucial role of myeloid cell-specific ErbB3 signaling in the cardiac accumulation of myeloid cells, which contributes to the activation of cardiac endothelial cells and fibroblasts and development of an early adaptive response to cardiac pressure overload in male mice. Graphical abstract: Unlabelled Image Highlights: The level of ErbB3 cell surface expression is higher on cardiac myeloid cells compared to cells in the blood and spleen Transverse aortic constriction induced rapid, within three days after surgery, accumulation of myeloid cells in the heart Genetic ablation of ErbB3 in myeloid cells resulted in the development of acute heart failure in male but not female mice ErbB3 deletion was associated with reduced accumulation of myeloid cells in the hearts of male but not female mice NRG-1, an ErbB receptor ligand, induced migration in myeloid cells from control animals but not from mice with ErbB3 deletion