PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK-CREB-Mfn2-mitophagy signaling pathway.
J Cell Physiol
; 235(5): 4878-4889, 2020 05.
Article
in En
| MEDLINE
| ID: mdl-31654396
ABSTRACT
Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMP-activated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Coronary Artery Disease
/
Mitochondrial Proteins
/
PTEN Phosphohydrolase
/
CREB-Binding Protein
/
AMP-Activated Protein Kinases
/
Human Umbilical Vein Endothelial Cells
/
Mitophagy
/
GTP Phosphohydrolases
/
Lipoproteins, LDL
/
Mitochondria
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Cell Physiol
Year:
2020
Type:
Article
Affiliation country:
China