AUTHOR=Xu Mingxi , Zheng Xu , Wang Dongxia , Fu Xiaodan , Xing Yida , Liu Yu , Wang Hongjiang , Kong Xiaodan TITLE=Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling JOURNAL=Frontiers in Physiology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.700338 DOI=10.3389/fphys.2021.700338 ISSN=1664-042X ABSTRACT=

Hyperuricemia-induced cardiac remodeling is at least in part via pressure-dependent mechanisms, yet the pressure-independent mechanisms are not well understood. C-X-C motif chemokine ligand 1 (CXCL1) was upregulated in renal tubules from mice subjected to uric acid (UA)-induced nephropathy. Given that CXCL1 is a master chemokine responsible for the recruitment of macrophage by binding with its receptor C-X-C motif chemokine receptor 2 (CXCR2), we thus hypothesized that UA-induced cardiac injury is via promoting the recruitment of CXCR2 + macrophages into the heart, which enhances cardiac inflammation. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured the level of cardiac CXCL1. We also tested the efficacy of the CXCR2 antagonist on UA-induced cardiac inflammation and remodeling. We found a high plasma level of UA-induced upregulation of CXCL1 in heart tissues. CXCR2 antagonist relieved UA-induced cardiac hypertrophy and suppressed cardiac inflammation and fibrosis. The silencing of CXCR2 in human monocytes abolished the migration of UA-induced monocyte. Thus, the interventions against CXCL1/CXCR2 may be effective for the prevention and treatment of UA-induced cardiac hypertrophy and inflammatory responses.