miR-199b-5p-AKAP1-DRP1 Pathway Plays a Key Role in ox-LDL-induced Mitochondrial Fission and Endothelial Apoptosis.

Abstract

BACKGROUND:

Atherosclerosis (AS) remains prevalent despite hyperlipidemia-lowering therapies. Although multiple functions of miR-199b-5p have been implicated in cancers, its role in endothelial apoptosis and AS remains unclear. This study aimed to examine the role of miR-199b-5p in mitochondrial dynamics and endothelial apoptosis.

METHODS:

Human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) were subjected to other treatments, followed by a series analysis. We found that ox-LDL-treated HUVECs were associated with miR-199b-5p downregulation, increased reactive oxygen species level, reduced adenosine triphosphate (ATP) production, mitochondrial fission, and apoptosis, whereas enhanced miR-199b-5p expression or applied mitochondrial division inhibitor 1 (Mdivi-1) markedly reversed these changes.

RESULTS:

Mechanistically, A-kinase anchoring protein 1 (AKAP1) was confirmed as a downstream target of miR-199b-5p by dual-luciferase activity reporter assay. AKAP1 overexpression reversed the anti-apoptotic effects of miR-199b-5p through the enhanced interaction of AKAP1 and dynamin protein 1 (DRP1) in ox-LDL-treated HUVECs. Moreover, miR-199b-5p downregulation, AKAP1 upregulation, and excessive mitochondrial fission were verified in human coronary AS endothelial tissues.

CONCLUSION:

The miR-199b-5p-dependent regulation of AKAP1/DRP1 is required to inhibit hyperlipidemia- induced mitochondrial fission and endothelial injury and may be a promising therapeutic target for AS.

• Authors: Xiaolei Cui, Yingping Tian, Yapei Zhao, Hengbo Gao, Dongqi Yao, Liang Liu, Yongjun Li
• Journal: Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 23 Issue 13 Pg. 1612-1622 ( 2022) ISSN: 1873-4316 [Electronic] Netherlands
• PMID: 35331106 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• A Kinase Anchor Proteins
• Lipoproteins, LDL
• MicroRNAs
• Reactive Oxygen Species
• oxidized low density lipoprotein
• Adenosine Triphosphate
• Luciferases
• Dynamin I
• Dynamins

Topics

• A Kinase Anchor Proteins (metabolism, pharmacology)
• Adenosine Triphosphate (metabolism, pharmacology)
• Apoptosis
• Atherosclerosis (metabolism)
• Dynamin I (metabolism)
• Dynamins (genetics, metabolism, pharmacology)
• Human Umbilical Vein Endothelial Cells
• Humans
• Lipoproteins, LDL (pharmacology)
• Luciferases (metabolism, pharmacology)
• MicroRNAs (genetics, metabolism)
• Mitochondrial Dynamics
• Reactive Oxygen Species (metabolism)