Details

Autor(en) / Beteiligte

• Feng, Xiaochao
• Zheng, Xixi
• Lin, Aiqi
• Yang, Shilin
• Zhang, Shufan
• Wu, Danhong
• Wu, Weicheng
• Han, Xiang

Titel

FBN1 knockout promotes cervical artery dissection by inducing N-glycosylation alternation of extracellular matrix proteins in rat VSMCs

Ist Teil von

• Cellular signalling, 2023-10, Vol.110, p.110834-110834, Article 110834

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2023

Quelle

ScienceDirect

Beschreibungen/Notizen

• FBN1 mutation promotes the degeneration of microfibril structures and extracellular matrix (ECM) integrity in the tunica media of the aorta in Marfan syndrome. However, whether FBN1 modulates cervical artery dissection (CAD) development and the potential molecular mechanisms of abnormal FBN1 in CAD remains elusive. In this study, FBN1 deficiency participated in the development of CAD and influenced the proliferation, apoptosis, and migration of vascular smooth muscle cells. FBN1 knockout induced alternations in mRNA levels of the transcriptome, protein expression of the proteome, and abundance of N-glycosylation of the N-glycoproteome. Comprehensive analysis of multiple omics showed up-regulation in mRNA levels of ECM proteins; yet, both the ECM protein levels and relative abundance of N-glycosylation were decreased. Moreover, we performed in vivo experiments to confirm the altered glycosylation of proteins in vascular smooth muscle cells. In conclusion, FBN1 deletion in vascular smooth muscle cells can result in altered N-glycosylation of ECM protein, which were critical for the stability of ECM and the process of CAD. This may open the way for a novel therapeutic strategy to treat people with CAD. [Display omitted] •Deficient FBN1 induces the onset of cervical artery dissection.•FBN1 mediates the function of extracellular matrix and vascular smooth muscle cells in cervical artery dissection.•FBN1 deletion results in altered N-glycosylation of ECM protein.