Genetic deletion of CXCL10 in mice attenuated cardiac remodeling, reduced hypertrophy and fibrosis, and protected against cardiac dysfunction 6 weeks after transverse aortic constriction.
Does genetic deletion of CXCL10 prevent pressure overload-induced cardiac remodeling and heart failure progression in mice?
CXCL10 from recruited macrophages accelerates pathologic cardiac remodeling, suggesting that targeting CXCL10 could be a novel therapeutic strategy for inflammation-driven heart failure.
Heart failure is a syndrome where immune cells play a crucial role in its development and progression. Although the recruitment of T cells driven by C-X-C motif chemokine receptor 3 activation has been reported, the specific contribution of C-X-C motif chemokine ligand 10 (CXCL10), one of its ligands, remains unclear. Here, we investigate the role of CXCL10 in pressure overload–induced cardiac remodeling, both in the early phase of remodeling and during heart failure progression. We used the transverse aortic constriction model to induce pressure overload in mice and assessed the role of CXCL10 in cardiac remodeling. Our study shows that the genetic deletion of CXCL10 attenuates early cardiac remodeling and with more pronounced effects 6 weeks after transverse aortic constriction, as CXCL10–/– mice exhibit reduced hypertrophy and fibrosis and are protected from the development of cardiac dysfunction, which was observed in wild-type animals. Notably, CXCL10–/– mice do not show T-cell expansion and activation in the draining lymph nodes, particularly in the CD4+ T-cell subset. Using bone marrow chimeras, we show that CXCL10 from recruited macrophages accelerates pathologic cardiac remodeling. Our findings establish CXCL10 as a key mediator of heart failure, acting through immune cell recruitment and activation. These results suggest that targeting CXCL10 could provide a novel therapeutic strategy to mitigate inflammation-driven heart failure progression.
Souza-Neto et al. (Sun,) conducted a other in Pressure overload-induced heart failure. Genetic deletion of CXCL10 vs. Wild-type animals was evaluated on Cardiac remodeling, hypertrophy, fibrosis, and cardiac dysfunction. Genetic deletion of CXCL10 in mice attenuated cardiac remodeling, reduced hypertrophy and fibrosis, and protected against cardiac dysfunction 6 weeks after transverse aortic constriction.