AUTHOR=Wang Yi , Bai Linnan , Wen Jiejun , Zhang Fangfei , Gu Sijie , Wang Feng , Yin Jianyong , Wang Niansong 

TITLE=Cardiac-specific renalase overexpression alleviates CKD-induced pathological cardiac remodeling in mice

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1061146

DOI=10.3389/fcvm.2022.1061146

ISSN=2297-055X

ABSTRACT=CKD-induced pathological cardiac remodeling is characterized by myocardial hypertrophy and cardiac fibrosis. The available therapeutic options are limited, it is thus urgently needed to identify novel therapeutic targets. Renalase (RNLS) is a newly discovered protein secreted by the kidney and was found beneficial in many renal diseases. But whether it exerts protective effects on cardiac remodeling in CKD remains unclear. In this study, we examined the cardioprotective role of RNLS in CKD-induced cardiac remodeling by using RNLS knockout mice and an adeno-associated virus (AAV9) system to overexpress RNLS cardiac specifically. The results showed that knockout of RNLS aggravated cardiac remodeling in CKD. In contrast, RNLS overexpression significantly attenuated the thickening of the left ventricular wall and interventricular septum and significantly reduced cardiac fibrosis. The following RNA-sequencing analysis revealed that RNLS significantly downregulated the extracellular matrix (ECM) receptor interaction pathway. GSEA results showed RNLS significantly downregulated several profibrotic biological processes of cardiac fibroblasts that were upregulated by CKD, including fibroblast proliferation, leukocyte migration, antigen presentation, cytokine production, and epithelial-mesenchymal transition (EMT). In vitro, we validated that RNLS reduced the primary cardiac fibroblast proliferation and α-SMA expression stimulated by TGF-β. In conclusion, RNLS may be a potential therapeutic factor that exerts an anti-fibrotic effect in pathological cardiac remodeling.