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Down-regulating of MFN2 promotes vascular calcification via regulating RAS-RAF-ERK1/2 pathway.
Zhang, Wen-Bo; Feng, Si-Yi; Xiao, Zhan-Xiang; Qi, You-Fei; Zeng, Zhao-Fan; Chen, Hao.
Afiliación
  • Zhang WB; Department of Vascular Surgery, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou 570311, Hainan Province, PR China. Electronic address: webozha789@163.com.
  • Feng SY; Department of Ultrasound Medicine, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou 570311, Hainan Province, PR China.
  • Xiao ZX; Department of Vascular Surgery, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou 570311, Hainan Province, PR China.
  • Qi YF; Department of Vascular Surgery, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou 570311, Hainan Province, PR China.
  • Zeng ZF; Department of Vascular Surgery, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou 570311, Hainan Province, PR China.
  • Chen H; Department of Vascular Surgery, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou 570311, Hainan Province, PR China.
Int J Cardiol ; 366: 11-18, 2022 11 01.
Article en En | MEDLINE | ID: mdl-35716948
BACKGROUND: Vascular calcification (VC), as a prevalent feature of atherosclerosis (AS), is a life-threatening pathological change. Mitofusin 2 (MFN2) has been reported to be down-regulated and participate in the pathogenesis of AS. Here, we explored the feasible impacts of MFN2 on VC in AS. METHODS: Atherosclerotic lesion was evaluated by Oil Red O staining. The VC was detected by Alizarin Red S staining, ALP staining, and calcium content in vascular smooth muscle cells (VSMCs) or atherosclerotic mice. The chondrocyte differentiation of VSMCs was measured by Alcian blue staining. Western blotting and qRT-PCR were used to determine the protein and mRNA expression of associated molecules. Intermolecular interaction was measured by ChIP and dual luciferase assays. RESULTS: The expression of MFN2 and E2F1 was reduced in the aorta tissues of AS patients and mice. Silencing of MFN2 drove calcification in VSMCs and aortas of atherosclerotic mice as confirmed by up-regulating RUNX2, OPG levels, and down-regulating SM22α, α-SMA levels. The chondrocyte differentiation of VSMCs was accelerated by MFN2 knockdown through inducing the expression of Aggrecan, Collagen II, and SOX9. In addition, E2F1 promoted the transcription and expression of MFN2 in VSMCs. Overexpression of MFN2 or E2F1 suppressed ox-LDL-induced VSMC calcification. Finally, MFN2 depletion enhanced VSMC calcification via activating RAS-RAF-ERK1/2 pathway. CONCLUSION: Our results suggest that silencing of MFN2 drives VC via activating RAS-RAF-ERK1/2 pathway in the progression of AS, thus MFN2 may be a therapeutic target for AS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Calcificación Vascular Límite: Animals Idioma: En Revista: Int J Cardiol Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Calcificación Vascular Límite: Animals Idioma: En Revista: Int J Cardiol Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos