Chuanfu Li, MD, and Kun Yang, MD, PhD, are corresponding authors in a new publication
in Frontiers in Immunology exploring the role of endothelial-specific heat shock protein
A12B (HSPA12B) in regulating monocyte infiltration post cardiac injury.
The article, titled “Endothelial HSPA12B regulates myocardial monocyte infiltration and inflammatory activity after myocardial infarction,” investigates the critical interplay between endothelial cells and cardiac immune responses. The scientists found that the endothelial HSPA12B plays a protective role after myocardial infarction (MI). Mice deficient in endothelial HSPA12B exhibited worsened cardiac function and increased monocyte infiltration compared to wild-type controls. Remarkably, HSPA12B was found to be secreted via endothelial exosomes and taken up by macrophages, shifting them from a pro-inflammatory to a reparative phenotype.
Inflammation is a double-edged sword in cardiac injury. While necessary for initiating repair, excessive or prolonged inflammation drives pathological remodeling. The findings highlight a novel mechanism by which endothelial cells can modulate immune cell behavior through exosome release. Mechanistically, the exosomal HSPA12B induced ubiquitination and degradation of toll-like receptor 4 (TLR4) and MyD88 in macrophages, suppressing NF-κB activation and pro-inflammatory cytokine release. Dr. Li's laboratoy group has previously reported in JCI Insight that endothelial HSPA12B enhances angiogenesis following MI. The first author of these two publications, Dr. Min Fan, said “Our findings identify that endothelial HSPA12B is a critical regulator governing the cardiac remodeling after injury. HSPA12B is required not only to enhance angiogenesis but also maintain the inflammation homeostasis.”
Dr. Li is a professor and Dr. Yang is an assistant professor in the Department of Surgery. Both are CIIDI members.
Authors (CIIDI members are in BOLD): Yana Wang, Min Fan, Linjian Chen, P. Spencer Gill, Xiaohui Wang, Tuanzhu Ha, David L. Williams, Chuanfu Li, Kun Yang
