HMGB1 in macrophage nucleus protects against pressure overload induced cardiac remodeling via regulation of macrophage differentiation and inflammatory response.

Abstract

Pressure overload induced cardiac remodeling is associated with a complex spectrum of pathophysiological mechanisms. As inflammatory cells, macrophages maintain a critical position in mechanical stress-induced myocardial remodeling. HMGB1 is a highly conserved, ubiquitous protein in various types of cells whose biological roles are closely dependent on subcellular sites. However, whether HMGB1 expressed in macrophages performs the protective or pathological responses in cardiac remodeling is unknown. In this study, we generated the myeloid-specific HMGB1 knockout mice and detected the effects of macrophage HMGB1 in response to pathophysiological stress. Our data showed HMGB1 in macrophages played a protective role against the pressure overload induced cardiac pathophysiology. The deletion of HMGB1 in macrophages gains more differentiation of M1-type pro-inflammatory macrophage during the mechanical stress-induced myocardial remodeling, thereby aggravating the inflammatory response in whole heart, resulting in accelerated deterioration of cardiac function. Moreover, in vitro data also validated HMGB1 got involved in the process of macrophage polarization. Macrophages without HMGB1 are more inclined to differentiate into M1 during the stretch process. In summary, the present results indicated that loss of HMGB1 in macrophages can exacerbate heart failure through increased differentiation of pro-inflammatory macrophages and enhanced inflammatory response.

• Authors: Xue Yang, Baoli Zhang, Peng Yu, Ming Liu, Chunyu Zhang, Enyong Su, Shiyao Xie, Yunzeng Zou, Hong Jiang, Junbo Ge
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 611 Pg. 91-98 (06 30 2022) ISSN: 1090-2104 [Electronic] United States
• PMID: 35483224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• HMGB1 Protein
• HMGB1 protein, mouse

Topics

• Animals
• HMGB1 Protein (metabolism)
• Heart
• Macrophages (metabolism)
• Mice
• Myocardium (metabolism)
• Ventricular Remodeling (physiology)