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:Thoracic aortic aneurysm (TAA) is a perilous disease that can lead to aortic dissection (AD), the pathophysiological mechanisms of which remain largely elusive. To improve our understanding of the molecular mechanism underlying TAA, we conducted a tandem mass tag (TMT)-based proteomics analysis and identified two down-regulated proteins, integrin αV, and integrin αL, in serum samples from patients with type A aortic dissection. We confirmed that integrin αV is extensively expressed in the aortic media, and its expression decreases after dissection, whereas the expression of integrin αL showed no significant alteration. Subsequently, by employing a mouse model of TAA induced by β-Aminopropionitrile (BAPN), we discovered that the mice treated with integrin αV inhibitors Cilengitide or SB273005 developed dramatically expansive ascending TAA, accompanied by exacerbated disorganization or loss of elastic fibers. Bulk RNA sequencing results further indicated that the treatment with integrin αV inhibitors exacerbates the pro-inflammatory response in mouse TAA development. These data suggest that integrin αV may be a novel target for TAA intervention. However, it also raises concerns about exposure to integrin αV inhibitors, which are conducted in serious cancer clinical trials, may pose a potential risk of developing aortic aneurysm (AA)/AD.
Project description:Thoracic aortic aneurysm (TAA) is a perilous disease that can lead to aortic dissection (AD), the pathophysiological mechanisms of which remain largely elusive. To improve our understanding of the molecular mechanism underlying TAA, we conducted a tandem mass tag (TMT)-based proteomics analysis and identified two down-regulated proteins, integrin αV, and integrin αL, in serum samples from patients with type A aortic dissection. We confirmed that integrin αV is extensively expressed in the aortic media, and its expression decreases after dissection, whereas the expression of integrin αL showed no significant alteration. Subsequently, by employing a mouse model of TAA induced by β-Aminopropionitrile (BAPN), we discovered that the mice treated with integrin αV inhibitors Cilengitide or SB273005 developed dramatically expansive ascending TAA, accompanied by exacerbated disorganization or loss of elastic fibers. Bulk RNA sequencing results further indicated that the treatment with integrin αV inhibitors exacerbates the pro-inflammatory response in mouse TAA development. These data suggest that integrin αV may be a novel target for TAA intervention. However, it also raises concerns about exposure to integrin αV inhibitors, which are conducted in serious cancer clinical trials, may pose a potential risk of developing aortic aneurysm (AA)/AD.
Project description:The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. We found that miR-1204 was significantly increased in both plasma and aorta of elder patients with AAD, and was positively correlated with age. Cell senescence induced the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induced vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop.
Project description:Conducted proteomics on samples from patients with aortic aneurysm and from non-dilated controls. Furthermore, we investigated both patients with bicuspid aortic valves (BAV) and also the more normal tricuspid aortic valves (TAV). The aim was to elucidate the molecular mechanisms behind the higher propensity of BAV patients to develop aorta dilation and consequent aortic aneurysm.
Project description:Although abnormal TGFbeta signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, the precise role of TGFbeta signaling in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to investigate the role of TGFbeta signaling in molecular pathways of pathogenesis associated with development of aortic aneurysm and aortic rupture. This study reports an isoform-specific effect of TGFbeta in MFS aortic disease and the effects of deleting the first hybrid domain of fibrillin-1 on TGFbeta signaling. Distinct molecular differences in mouse models of aneurysm (Fbn_GT-8_plus), of aneurysm and rupture (Fbn1_GT-8_H1delta), and of microdissection (Fbn1_H1delta_plus) were identified, which associated with TGFbeta signaling and extracellular matrix composition, possibly contributing to the development of dissection and rupture. These findings offer new insights into the pathophysiological mechanisms that potentially drive initiation of aortic dissection and could pave the way for development of new treatment targets of aortic disease.
Project description:To determine how gene expression is altered in aorta tissue in response to aortic aneurysm disease. Thoracic or abdominal aorta tissue was isolated from patients requiring surgery due to aortic aneurysm or other (control) reason.
Project description:Conducted proteomics on samples from patients with aortic aneurysm and from non-dilated controls. Furthermore, we investigated both patients with bicuspid aortic valves (BAV) and also the more normal tricuspid aortic valves (TAV). The aim was to elucidate the molecular mechanisms behind the higher propensity of BAV patients to develop aorta dilation and consequent aortic aneurysm.
Project description:The aim of this study was to assess the relative gene expression in human AAA and AOD. Genome-wide expression analysis of abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) specimens obtained from 20 patients with small AAA (mean maximum aortic diameter=54.3±2.3 mm), 29 patients with large AAA (mean maximum aortic diameter=68.4±14.3 mm), and 9 AOD patients (mean maximum aortic diameter=19.6±2.6 mm). Relative aortic gene expression was compared with that of 10 control aortic specimen of organ donors.
Project description:To discover novel biomarkers for aortic aneurysm, serum samples of patients with thoracic aortic aneurysm were fractionated, tryptic digested, and subjected to proteome analysis.