Macrophage-mediated downregulation of lncRNA Carmn in mouse abdominal aortic aneurysm

In this study, we analyzed publicly available single-cell or bulk RNA sequencing data comparing healthy and aneurysmal mouse aortic tissues. In both healthy and diseased aortas, Carmn expression was enriched in SMCs characterized by the high expression of SMC-specific contractile proteins including Myh11 and Acta2. Carmn expression levels varied among the sub-clusters of SMCs and consequently along the aortic tree. Comparing to the corresponding sham aorta, aortas from 3 distinct AAA models contained less Carmn. To validate the Carmn downregulation, we induced AAA using the Angiotensin II and CaCl2 models. In situ hybridization showed that Carmn mRNA located in the nuclei of SMCs and became downregulated within a few days following the aneurysm induction. Mechanistically, we tested whether Carmn expression is regulated by infiltrating macrophages --- the predominant inflammatory cells found in aneurysmal tissues --- by treating healthy mouse aortic SMCs with media conditioned by macrophages primed with pro-inflammatory or anti-inflammatory cytokines. PCR analysis showed that inflammatory macrophages reduced the expression of Carmn and contractile genes including Myh11 and Acta2. Taken together, our results from bioinformatic and experimental analyses demonstrate that Carmn is downregulated in different AAA models, likely by inflammatory macrophages. The negative regulation of Carmn in AAA tissues may explain at least in part the loss of SMC contractile state during the pathog...
Source: Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research