Open AccessmiR‐145 attenuates phenotypic transformation of aortic vascular smooth muscle cells to prevent aortic dissection
Author(s) -
Qiu ZhiHuang,
He Jian,
Chai Tianci,
Zhang Yuling,
Zhou Hao,
Zheng Hui,
Chen Xiaosong,
Zhang Li,
Li Yumei,
Chen Liangwan
Publication year - 2021
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23773
Subject(s) - downregulation and upregulation , phenotype , vascular smooth muscle , phenotypic switching , klf4 , microbiology and biotechnology , microrna , transformation (genetics) , aorta , biology , chemistry , medicine , smooth muscle , endocrinology , gene , sox2 , biochemistry , transcription factor
Background miR ‐ 145 is closely related to vascular smooth muscle cells (VSMC) phenotype transformation; however, the regulatory mechanisms through which miR ‐ 145 regulates the VSMC phenotype transformation under mechanical stretching are unclear. In this study, we evaluated the roles of miR ‐ 145 in VSMCs subjected to mechanical stretching in aortic dissection (AD). Methods The expression of miR‐145 in the aortic vessel wall of model animals and patients with AD was analyzed by quantitative polymerase chain reaction. miR‐145‐related protein‐protein interaction networks and Wikipathways were used to analyze VSMC phenotypic transformation pathways regulated by miR‐145. We used gain‐ and loss‐of‐function studies to evaluate the effects of miR‐145 on VSMC differentiation under mechanical stretch induction and assessed whether Krüppel‐like factor 4 (KLF4) was regulated by miR‐145 in the aorta under mechanical stretch conditions. Results miR ‐ 145 was abundantly expressed in the walls of the normal human aorta, but was significantly downregulated in animal models and the walls of patients with dissection. We found that contractile phenotype‐related proteins were downregulated in VSMCs subjected to mechanical stretching, whereas the expression of secreted phenotype‐related proteins increased. miR ‐ 145 overexpression also downregulated contractile phenotype‐related proteins in VSMCs and suppressed upregulation of phenotype‐related proteins. Finally, under mechanical stretching, KLF4 expression was significantly increased in VSMCs, and overexpression of miR ‐ 145 blocked this effect. Conclusion Our results confirmed that mechanical stretch‐induced phenotypic transformation of VSMCs to promote AD via upregulation of KLF4; this mechanism was regulated by miR ‐ 145 , which directly modulated KLF4 expression and VSMC differentiation.