ISSN 2149-2263 | E-ISSN 2149-2271 Home      
 
Volume : 23 Issue : 1
Current Issue Archive Popular Article Ahead of Print

   
Quick Search





 
Advanced glycation end products facilitate proliferation and reduce early apoptosis of cardiac microvascular endothelial cell via PKCβ signaling pathway: insight from diabetic cardiomyopathy [Anatol J Cardiol]
Anatol J Cardiol. Ahead of Print: AJC-21504 | DOI: 10.14744/AnatolJCardiol.2019.21504  

Advanced glycation end products facilitate proliferation and reduce early apoptosis of cardiac microvascular endothelial cell via PKCβ signaling pathway: insight from diabetic cardiomyopathy

Yi Luan, Jiefang Zhang, Min Wang, Guosheng Fu, Wenbin Zhang
Department Of Cardiology, Biomedical Research (therapy) Center, Sir Run Run Shaw Hospital, College Of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

Objective:To investigate the effects of advanced glycation end products (AGEs) on the proliferation and apoptosis of cardiac microvascular endothelial cells (CMECs) in rats and its underlying signaling pathway.
Methods: CMECs were isolated from Sprague-Dawley rats. We first examined the effects of AGEs on proliferation and apoptosis of CMECs, then tested whether protein kinase C (PKC) β blockers could counteract the effects of AGEs. PKC agonists PMA and PKCβ blockers were also used to verify whether PKC could act independently on CMECs. Receptor for AGEs (RAGE)-siRNA transfection was used to verify the effect of AGEs on PKC. Through the above steps, we explained whether AGEs regulated CMEC proliferation and early apoptosis through PKCβ signaling pathway. Proliferation of CMECs was detected by Cell Counting Kit-8 (CCK-8) assay, and early apoptosis was determined by Annexin V-FITC/PI double staining. Expression of proliferation and apoptosis-related proteins and PKC phosphorylation were determined by western blotting analysis. Cell cycle distributions were assayed using a BD FACS calibur cell sorting system.
Results: AGEs facilitated the proliferation of CMECs, up-regulated p-ERK, and accelerated the entry of cells from G1 phase to S + G2/M phase, which was consistent with the up-regulated cyclin D1 by AGEs. AGEs inhibited early apoptosis of CMECs by increasing the expression of survivin and decreasing the expression of cleaved-caspase3. All of these effects can be reversed by PKCβ1/2inhibitors. In addition, AGE upregulated RAGE expression and phosphorylation of PKCβ1/2 in CMECs while inhibition of RAGE reversed the phosphorylation as well as the effects of AGEs on proliferation and apoptosis in CMECs.
Conclusion: The study indicated that AGEs facilitated proliferation and reduced early apoptosis of CMECs via PKCβ signaling pathway.

Keywords: advanced glycation end products, cardiac microvascular endothelial cells, diabetic cardiomyopathy, protein kinase C




Corresponding Author: Wenbin Zhang, China


TOOLS
Print
Download citation
RIS
EndNote
BibTex
Medlars
Procite
Reference Manager
Share with email
Share
Send email to author

Similar articles
PubMed
Google Scholar




 
 
KARE Publishing | Copyright 2018 Turkish Society of Cardiology