miR-145-5p affects autophagy by targeting CaMKIIδ in atherosclerosis

Atherosclerosis (AS) is a chronic progressive inflammatory disease involving many cells. miR-145-5p mediates the biological phenotypes of human aortic vascular smooth muscle cells (HAVSMCs) and influences the progression of AS, but the potential mechanism needs further study. Total RNA was extracted...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:International journal of cardiology 2022-08, Vol.360, p.68-75
Hauptverfasser: Zhang, Xinxin, Zai, Ling, Tao, Ziqi, Wu, Daiqian, Lin, Mingying, Wan, Jing
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Atherosclerosis (AS) is a chronic progressive inflammatory disease involving many cells. miR-145-5p mediates the biological phenotypes of human aortic vascular smooth muscle cells (HAVSMCs) and influences the progression of AS, but the potential mechanism needs further study. Total RNA was extracted from patient plasma and arteries to determine the expression of miR-145-5p. The CaMKIIδ pathway and genes were predicted as the target of miR-145-5p by bioinformatics approaches. The interaction between miR-145-5p and CaMKIIδ was confirmed by RT–qPCR and Dual Luciferase Reporter Assay System. Western blot analysis, immunofluorescence staining, transmission electron microscopy (TEM) and protein tracing on HAVSMCs transduced with mCherry-GFP-LC3 lentiviral vectors to determine the mechanism by which miR-145-5p affects the atherosclerotic disease process. The expression of miR-145-5p was downregulated in blood and arteries specimens of patients with coronary stenosis. Correspondingly, CaMKIIδ was upregulated and miR-145-5p was downregulated in hypoxic HAVSMCs. CaMKIIδ was predicted and confirmed as a downstream target of miR-145-5p. In addition, CaMKIIδ induced the upregulation of autophagy-related proteins by activating the AMPK/mTOR/ULK1 signalling pathway. Moreover, we confirmed that miR-145-5p inhibits CaMKIIδ expression by binding to a specific sequence in the CaMKIIδ 3′ UTR and affects autophagy. Crucially, CaMKIIδ was promoted by the downregulation of miR-145-5p and then activating autophagy in HAVSMCs through the AMPK/mTOR/ULK1 signalling pathway to affect the AS progress. miR-145-5p regulates CaMKIIδ, leading to altered autophagy in HAVSMCs. This alteration plays an important role in AS progression. •Downregulation of miR-145-5p expression and upregulation of CaMKIIδ expression were found in patients with atherosclerosis.•miR-145-5p directly downregulates CaMKIIδ expression, leading to repressed autophagy in HAVSMCs.•miR-145-5p targets the CaMKIIδ to inhibit the AMPK/mTOR/ULK1 signalling pathway.
ISSN:0167-5273
1874-1754
DOI:10.1016/j.ijcard.2022.05.039