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- Title
Iron deficiency affects oxygen transport and activates HIF1 signaling pathway to regulate phenotypic transformation of VSMC in aortic dissection.
- Authors
Chen, Yuanyang; Li, Xu; Wang, Zhiwei; Yuan, Shun; Shen, Xiaoyan; Xie, Xiaoping; Xing, Kai; Zhu, Qingyi
- Abstract
Background: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. Methods: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. Results: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation. Highlights: This study demonstrated for the first time that ID can alter HIF1 transcription through oxygen transport and participate in the occurrence of AD. The promoting effect of ID on phenotypic transformation of VSMC may be through HIF1 signaling pathway. Specific inhibition of HIF1 can effectively alleviate the exacerbation of AD disease caused by ID and HIF1 may be an important target for drug therapy of AD.
- Subjects
PHENOTYPIC plasticity; AORTIC dissection; IRON deficiency; CELLULAR signal transduction; VASCULAR smooth muscle; IRON supplements
- Publication
Molecular Medicine, 2024, Vol 30, Issue 1, p1
- ISSN
1076-1551
- Publication type
Article
- DOI
10.1186/s10020-024-00859-y