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.
Highlights
Similar to other chemokine receptors, CC chemokine receptor 9 (CCR9) is a G-protein coupled receptor with only one known ligand, thymus-expressed chemokine/CCL2510
Immunohistochemistry indicated that CCL25 and CCR9 were mainly expressed in the infarct area and border zone, in which a large number of inflammatory cells had infiltrated, revealing that CCR9 was highly expressed in infiltrating cells
We originally showed that the abrogation of CCR9 improved cardiac structural remodeling and electrical remodeling in a murine model of Myocardial infarction (MI)
Summary
Similar to other chemokine receptors, CC chemokine receptor 9 (CCR9) is a G-protein coupled receptor with only one known ligand, thymus-expressed chemokine/CCL2510. CCR9 was found to be involved in the migration and development of T cells in the thymus[12]. Some studies have been conducted to interfere with the CCR9/ CCL25 axis and test its effectiveness. Other studies have shown that CCR9−/− mice are more susceptible to DSS-induced colitis[22,24]. Myocardial infarction is associated with inflammatory responses that involve a variety of chemokines[6]. It is unknown whether CCR9 plays a role in the post-MI pathological processes. We discovered that these beneficial outcomes were somehow dependent on the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
