Heart Failure Research Group, Baker Heart and Diabetes Institute, St Kilda Rd Central, PO Box 6492, Melbourne, VIC, 8008, Australia.
Biomarker Discovery, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Sci Rep. 2024 Nov 6;14(1):26985. doi: 10.1038/s41598-024-75789-0.
Cardiorenal fibrosis is a common feature of chronic cardiovascular disease and recent data suggests that cytokines and chemokines may also drive fibrosis. Here we tested the hypothesis that CXCR7, a highly conserved chemokine receptor, contributes to cardiac and renal fibrosis. We generated an anti-mouse CXCR7-specific monoclonal antibody (CXCR7 mAb) and tested its anti-fibrotic actions in cardiorenal fibrosis induced using the deoxycorticosterone acetate/uni-nephrectomy (DOCA-UNX) model. CXCR7 mAb treatment (10 mg/kg, twice weekly for 6 weeks) significantly attenuated the development of cardiac and renal fibrosis, and reduced fibrotic and inflammatory gene expression levels, in the absence of an effect on blood pressure. Immunohistochemical analysis demonstrated an increase in the vascular expression of CXCR7 in DOCA-UNX-treated mice. This study demonstrated that a CXCR7 mediated pathway plays a significant role in cardiac and renal fibrosis induced by DOCA-UNX treatment. Accordingly, antagonism of CXCR7 may provide a therapeutic opportunity to mitigate against fibrosis in the setting of mineralocorticoid excess.
心脏肾纤维化是慢性心血管疾病的常见特征，最近的数据表明细胞因子和趋化因子也可能导致纤维化。在这里，我们检验了这样一个假设，即趋化因子受体 CXCR7 是一种高度保守的趋化因子受体，可能促进心脏和肾脏纤维化。我们生成了一种抗小鼠 CXCR7 特异性单克隆抗体（CXCR7 mAb），并在使用醛固酮/单侧肾切除术（DOCA-UNX）模型诱导的心脏肾纤维化中测试了其抗纤维化作用。CXCR7 mAb 治疗（10mg/kg，每周两次，持续 6 周）显著减轻了心脏和肾脏纤维化的发展，并降低了纤维化和炎症基因表达水平，而对血压没有影响。免疫组织化学分析表明，在 DOCA-UNX 处理的小鼠中，血管中 CXCR7 的表达增加。这项研究表明，在 DOCA-UNX 治疗诱导的心脏和肾脏纤维化中，CXCR7 介导的途径起着重要作用。因此，CXCR7 的拮抗作用可能为对抗皮质激素过多引起的纤维化提供治疗机会。
