Maresin‐1 ameliorates hypertensive vascular remodeling through its receptor LGR6

Abstract

Hypertensive vascular remodeling is defined as the changes in vascular function and structure induced by persistent hypertension. Maresin‐1 (MaR1), one of metabolites from Omega‐3 fatty acids, has been reported to promote inflammation resolution in several inflammatory diseases. This study aims to investigate the effect of MaR1 on hypertensive vascular remodeling. Here, we found serum MaR1 levels were reduced in hypertensive patients and was negatively correlated with systolic blood pressure (SBP). The treatment of MaR1 reduced the elevation of blood pressure and alleviated vascular remodeling in the angiotensin II (AngII)‐infused mouse model. In addition, MaR1‐treated vascular smooth muscle cells (VSMCs) exhibited reduced excessive proliferation, migration, and phenotype switching, as well as impaired pyroptosis. However, the knockout of the receptor of MaR1, leucine‐rich repeat‐containing G protein‐coupled receptor 6 (LGR6), was seen to aggravate pathological vascular remodeling, which could not be reversed by additional MaR1 treatment. The mechanisms by which MaR1 regulates vascular remodeling through LGR6 involves the Ca2+/calmodulin‐dependent protein kinase II/nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 signaling pathway. Overall, supplementing MaR1 may be a novel therapeutic strategy for the prevention and treatment of hypertension.

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

“…Signaling pathways include signaling by GPCR [56] and extracellular matrix organization [57] were responsible for advancement of HD. Research has shown that CBLN2 [58], MOG (myelin oligodendrocyte glycoprotein) [59], ROS1 [60], LGR6 [61], GJA5 [62], SUCNR1 [63], REN (renin) [64], VEGFC (vascular endothelial growth factor C) [65], TLR2 [66], FGF12 [67], WT1 [68], SLC22A3 [69], CSRP3 [70], PAPPA2 [71], ACAN (aggrecan) [72], SHH (sonic hedgehog signaling molecule) [73], PDC (phosducin) [74], AGTR1 [75], XDH (xanthine dehydrogenase) [76], P2RX7 [77], NTSR1 [78], SIRT2 [79], RBP4 [80], BMP2 [81], ERBB3 [82], HAS2 [83], CDH13 [84], CSMD1 [85], NR3C2 [86], EPAS1 [87], TRPC6 [88], MMP3 [89], ERAP2 [90], HLA-DRB1 [91], CD74 [92], VWF (von Willebrand factor) [93], MTTP (microsomal triglyceride transfer protein) [494], ANGPT2 [184], AKR1C3 [495], NEDD4L [496], CASP1 [497], LDB2 [498], CHRNA5 [499], CCND2 [500], BRCA2 [97], ZBTB20 [501], EFNB2 [502], CYP7B1 [503], DCLK1 [504], RBM20 [505], PLCE1 [197], protein) [94], NEDD4L [95], CASP1 [96], BRCA2 [97], EFNB2 [98], PLCE1 [99], EGFR (epidermal growth factor receptor) [100], ABCA1 [101], CRHR2 [102], RND3 [103], COMT (catechol-O-methyltransferase) [104] and SMAD9 [105] plays an important role in the pathogenesis of hypertension. Studies have revealed that NEUROD4 [106], SOX10 [107], MOG (myelin oligodendrocyte glycoprotein) [108], NR5A2 [109], GLRA3 [110], FA2H [111], SERPINA […”