| http://purl.uniprot.org/citations/34041919 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34041919 | http://www.w3.org/2000/01/rdf-schema#comment | "Background Aortic dissection (AD) is one of the most life-threatening cardiovascular diseases that exhibit high genetic heterogeneity. However, it is unclear whether variants within the COL5A1 gene can cause AD. Therefore, we intend to determine whether COL5A1 is a causative gene of AD. Methods and Results We performed targeted sequencing in 702 patients with unrelated sporadic AD and 163 matched healthy controls using a predesigned panel with 152 vessel matrix-related genes. As a result, we identified that 11 variants in COL5A1 caused AD in 11 out of the 702 patients with AD. Furthermore, Col5a1 knockout (Col5a1+/-) rats were generated through the CRISPR/Cas9 system. Although there was no spontaneous AD, electron microscopy revealed a fracture of elastic fibers and disarray of collagenous fibers in 6-week-old Col5a1+/- rats, but not in WT rats (93.3% versus 0.0%, P<0.001). Three-week-old rats were used to induce the AD phenotype with β-aminopropionitrile monofumarate for 4 weeks followed by angiotensin II for 72 hours. The β-aminopropionitrile monofumarate and angiotensin II-treated rat model confirmed that Col5a1+/- rats had considerably higher AD incidence than WT rats. Subsequent mechanism analyses demonstrated that the transforming growth factor-β-signaling pathway was significantly activated in Col5a1+/- rats. Conclusions Our findings, for the first time, revealed a relationship between variants in COL5A1 and AD via targeted sequencing in 1.57% patients with sporadic aortic dissection. The Col5a1 knockout rats exhibited AD after an intervention, indicating that COL5A1 is a causative gene of AD. Activation of the transforming growth factor-β-signaling pathway may be implicated in the pathogenesis of this kind of AD."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.org/dc/terms/identifier | "doi:10.1161/jaha.120.019276"xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/author | "Chen P."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/author | "Sun Y."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/author | "Yu B."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/author | "Wang D.W."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/name | "J Am Heart Assoc"xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/pages | "e019276"xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/title | "pii>COL5A1pi/i> Variants Cause Aortic Dissection by Activating TGF-beta-Signaling Pathway."xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/34041919 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34041919 |
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