COL5A1 Variants Cause Aortic Dissection by Activating TGF‐β‐Signaling Pathway

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...

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Veröffentlicht in:Journal of the American Heart Association 2021-06, Vol.10 (11), p.e019276-e019276
Hauptverfasser: Chen, Peng, Yu, Bo, Li, Zongzhe, Chen, Yanghui, Sun, Yang, Wang, Dao Wen
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Sprache:eng
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Zusammenfassung: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
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.120.019276