ABSTRACT
Aortic dissection (AD) is a major cause of acute aortic syndrome with high mortality due to the destruction of aortic walls. Although recent studies indicate the critical role of inflammation in the disease mechanism of AD, it is unclear how inflammatory response is initiated. Here, we demonstrate that myocardin-related transcription factor A (MRTF-A), a signal transducer of humoral and mechanical stress, plays an important role in pathogenesis of AD in a mouse model. A mouse model of AD was created by continuous infusion of angiotensin II (AngII) that induced MRTF-A expression and caused AD in 4 days. Systemic deletion of Mrtfa gene resulted in a marked suppression of AD development. Transcriptome and gene annotation enrichment analyses revealed that AngII infusion for 1 day caused pro-inflammatory and pro-apoptotic responses before AD development, which were suppressed by Mrtfa deletion. AngII infusion for 1 day induced pro-inflammatory response, as demonstrated by expressions of Il6, Tnf, and Ccl2, and apoptosis of aortic wall cells, as detected by TUNEL staining, in an MRTF-A-dependent manner. Pharmacological inhibition of MRTF-A by CCG-203971 during AngII infusion partially suppressed AD phenotype, indicating that acute suppression of MRTF-A is effective in preventing the aortic wall destruction. These results indicate that MRTF-A transduces the stress of AngII challenge to the pro-inflammatory and pro-apoptotic responses, ultimately leading to AD development. Intervening this pathway may represent a potential therapeutic strategy.
Subject(s)
Aortic Dissection/genetics , Inflammation/genetics , Trans-Activators/genetics , Transcriptome/genetics , Aortic Dissection/chemically induced , Aortic Dissection/pathology , Angiotensin II/toxicity , Animals , Apoptosis/drug effects , Chemokine CCL2/genetics , Disease Models, Animal , Gene Expression Regulation/drug effects , Humans , Inflammation/chemically induced , Inflammation/pathology , Interleukin-6/genetics , Mice , Stress, Mechanical , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Cryoballoon ablation is a well-established therapeutic tool for paroxysmal atrial fibrillation (PAF). We herein report a rare case of a 69-year-old man with PAF undergoing hemodialysis due to chronic kidney disease who developed hyperkalemia caused by possible cold agglutinin disease during cryoballoon ablation therapy. During the procedure, his electrocardiogram showed wide QRS when we finished cryoablation therapy. We detected hyperkalemia and performed urgent hemodialysis. We should bear in mind that cold agglutinin disease can occur during cryoballoon ablation.
