Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction.

Abstract

CC chemokine receptor 9 (CCR9), which is a unique receptor for CC chemokine ligand (CCL25), is mainly expressed on lymphocytes, dendritic cells (DCs) and monocytes/macrophages. CCR9 mediates the chemotaxis of inflammatory cells and participates in the pathological progression of inflammatory diseases. However, the role of CCR9 in the pathological process of myocardial infarction (MI) remains unexplored; inflammation plays a key role in this process. Here, we used CCR9 knockout mice to determine the functional significance of CCR9 in regulating post-MI cardiac remodeling and its underlying mechanism. MI was induced by surgical ligation of the left anterior descending coronary artery in CCR9 knockout mice and their CCR9+/+ littermates. Our results showed that the CCR9 expression levels were up-regulated in the hearts of the MI mice. Abrogation of CCR9 improved the post-MI survival rate and left ventricular (LV) dysfunction and decreased the infarct size. In addition, the CCR9 knockout mice exhibited attenuated inflammation, apoptosis, structural and electrical remodeling compared with the CCR9+/+ MI mice. Mechanistically, CCR9 mainly regulated the pathological response by interfering with the NF-κB and MAPK signaling pathways. In conclusion, the data reveal that CCR9 serves as a novel modulator of pathological progression following MI through NF-κB and MAPK signaling.

• Authors: Yan Huang, Dandan Wang, Xin Wang, Yijie Zhang, Tao Liu, Yuting Chen, Yanhong Tang, Teng Wang, Dan Hu, Congxin Huang
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 32660 (09 02 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27585634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CC chemokine receptor 9
• NF-kappa B
• Receptors, CCR
• Mitogen-Activated Protein Kinase Kinases

Topics

• Animals
• Disease Models, Animal
• Gene Expression Profiling
• Mice, Knockout
• Mitogen-Activated Protein Kinase Kinases
• Myocardial Infarction (pathology)
• NF-kappa B (metabolism)
• Receptors, CCR (deficiency, metabolism)
• Signal Transduction
• Survival Analysis
• Ventricular Remodeling