Project description:Aortic dissection (AD) is a medical emergency that leads to sudden death. Effective medical therapy is not available because molecular mechanism of AD is poorly understood. We performed the transcriptome analysis in mouse AD model that was created by infusion of beta-aminopropionitrile, a collagen crosslink inhibitor, and angiotensin II. Bayesian network analysis of the transcriptome revealed several distinct gene clusters that were tightly co-regulated during AD development. Functional annotation analysis revealed that each gene cluster has distinct function, namely, cell proliferation, inflammation, cell locomotion and adhesion, and muscle differentiation. Among the gene clusters, cell proliferation cluster was the first to be activated during AD development. Cell proliferation before AD development was confirmed by immunoblotting of G1 cyclins. Immunostaining for Ki67 and cell markers revealed the proliferation of smooth muscle cells, fibroblasts, and monocytes in aortic tissue before AD development. Treatment of mice with rapamycin, an mTOR inhibitor, suppressed cell proliferative response in AD model. Rapamycin completely prevented AD when given before AD development, and effectively suppressed progression when given after AD development. Interestingly, transcriptome analysis showed that rapamycin strongly suppressed cell proliferation and muscle differentiation clusters, but its effect on inflammation cluster was modest. We concluded that mTOR constitutes an essential part of the molecular pathogenesis of AD by regulating cell proliferation, and represents a new therapeutic target.
Project description:Aneurysmatic and dissection cells show a specific alteration of gene expression, which allow a disease specific distinction. We used microarrays to analyse the cellular gene expression of controls, thoracic aortic aneurysm, and aortic dissection.
Project description:Genome wide DNA methylation profiling of ascending aorta tissue samples from normal, aortic dissection and bicuspid aortic valve patients with aortic dilation. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across more than 450,000 CpGs in ascending aorta samples. Samples included 6 normal donors, 12 patients with aortic dissection and 6 patients with bicuspid aortic valve and dilated aorta.
Project description:The mechanisms of acute aortic dissection are not well understood. Transcriptomic strategy has been proven to be an effective way to find the potential mechanisms and also the reliable biomarkers for a specific disease. The whole-genome expression profiling was assayed in a panel of aortic tissues from 4 male acute aortic dissection patients and 4 male healthy controls.
Project description:We investigated the relationship between a developemnt of aortic dissection and inflammatory cells. Il-1b high expression macrophage contributed to developing an aortic dissection.
Project description:Colchicine is an alkaloid found in the plant Colchicum, which is currently used for the treatment of acute gout and familial Mediterranean fever, and is being considered for the treatment of a variety of cardiovascular diseases such as pericarditis, atrial fibrillation, and coronary syndromes due to its significant anti-inflammatory effects. Aortic dissection is a cardiovascular disease characterised by a tear in the intima and congestion of the vessel wall leading to vessel wall delamination, with a rapid onset and high lethality. This study investigated the role of colchicine in BAPN-induced aortic dissection in mice. Gavage administration of colchicine along with BAPN modelling for three weeks showed a significant decrease in morbidity and mortality, indicating that colchicine can inhibit the occurrence of aortic dissection in mice.
Project description:Purpose: The aim of this study is to have a fullscape of molecular pathology of Stanford type A aortic dissection Methods: All TAAD patients under consideration underwent an ascending aortic replacement surgery during a cardiopulmonary bypass. The normal ascending aortic tissue samples were obtained from patients undergoing coronary artery bypass grafting surgery (CABG) without any aortic diseases. We selected 20 samples (10 TAAD and 10 normal) for the whole transcriptome sequencing. Total RNA was extracted from each sample using TRIzol Reagent (ThermoFisher) and was stored in 1 mL of 75% ethanol at -80 ℃ until further usage. Conclusions: We identified exaggerated autophagy as a molecular biomarker for aortic dissection. We also predicted 10 hub genes and an HIF1A-ATG3 axis which could provide new insights in understanding aortic dissection.
Project description:Genome wide DNA methylation profiling of normal and ascending aorta tissue samples from normal and aortic dissection patients. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,512 CpGs in ascending aorta tissue samples. Samples included 4 normal donors and 4 patients with aortic dissection.