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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
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CDC42 promotes vascular calcification in chronic kidney disease
Zehua Li1,2,3, Ji Wu1,2,3, Xiuli Zhang1,2,3
1Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.
The Journal of Pathology
|August 10, 2019
Summary
Cell division cycle 42 (CDC42) drives vascular calcification in chronic kidney disease (CKD) by promoting smooth muscle cell osteogenic differentiation. Inhibiting CDC42 may offer a new therapeutic strategy for treating vascular calcification.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Nephrology
Background:
- Vascular calcification is common in chronic kidney disease (CKD) and a significant cardiovascular disease risk factor.
- Vascular calcification involves osteogenic differentiation of vascular smooth muscle cells (VSMCs), similar to bone formation.
- Cell division cycle 42 (CDC42) is crucial for bone development, but its role in VSMC differentiation and vascular calcification is unknown.
Purpose of the Study:
- To investigate the role of CDC42 in VSMC osteogenic differentiation and vascular calcification.
- To explore the underlying molecular mechanisms, including the involvement of AKT signaling.
Main Methods:
- Assessed CDC42 expression in VSMCs and calcified rat arteries.
- Utilized adenovirus-mediated CDC42 overexpression and ML141 inhibition in vitro and ex vivo models.
- Investigated the effect of ML141 on vascular calcification in CKD rats.
- Examined the role of AKT signaling in CDC42-induced calcification.
Main Results:
- CDC42 expression was significantly increased in VSMCs and calcified arteries.
- CDC42 overexpression promoted VSMC calcification and upregulated bone-related markers (RUNX2, BMP2).
- CDC42 inhibition by ML141 blocked VSMC calcification in vitro, ex vivo, and in CKD rats.
- AKT signaling inhibition prevented CDC42-induced VSMC calcification.
Conclusions:
- CDC42 plays a critical role in promoting vascular calcification through VSMC osteogenic differentiation.
- CDC42-induced vascular calcification involves the AKT signaling pathway.
- CDC42 represents a potential therapeutic target for managing vascular calcification in CKD patients.
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