open access

Vol 83, No 1 (2024): Folia Morphologica
Original article
Submitted: 2022-10-31
Accepted: 2022-12-21
Published online: 2023-01-17
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FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling

Sanfu Zheng1, Yu Wang2, Weixi Guo3, Hongyu Tan4
·
Pubmed: 36688407
·
Folia Morphol 2024;83(1):125-138.
Affiliations
  1. Department of Cardiology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  2. Department of Ultrasound, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  3. Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
  4. Department of Internal Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

open access

Vol 83, No 1 (2024): Folia Morphologica
ORIGINAL ARTICLES
Submitted: 2022-10-31
Accepted: 2022-12-21
Published online: 2023-01-17

Abstract

Background: C1q/TNF-related protein 3 (CTRP3) has been clarified to display its protective roles in cardiac function. The current study is concentrated on exploring the impacts of CTRP3 on myocardial ischaemia.

Materials and methods: Oxygen and glucose hypoxia/reoxygenation (OGD/R) model was constructed in human cardiac microvascular endothelial cells (HCMECs). Reverse transcription-quantitative polymerase chain reaction and western blot analysis of CTRP3 expression were conducted. CCK-8 assay was to estimate cell activity and lactate dehydrogenase (LDH) assay kit was to test LDH release. TUNEL assay and western blot were to judge apoptosis. Endothelial barrier function was detected by in vitro vascular permeability assay kit. Zonula occludens-1 (ZO-1) expression was evaluated by immunofluorescence assay. The interaction between CTRP3 promoter and Forkhead Box O6 (FOXO6) was predicted by JASPAR database and verified by chromatin immunoprecipitation and luciferase reporter assays. After OGD/R-induced HCMECs were co-transfected with CTRP3 overexpression and FOXO6 overexpression plasmids, the above functional experiments above were conducted again. Lastly, the expression of sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling-related proteins was examined by western blot.

Results: CTRP3 was down-regulated in OGD/R-induced HCMECs. CTRP3 enhanced the viability and barrier integrity while reduced the apoptosis and permeability of OGD/R-insulted HCMECs. This process may be regulated by FOXO6 transcription. Also, FOXO6 inhibition-mediated CTRP3 up-regulation activated the SIRT1/Nrf2 signalling.

Conclusions: FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling.

Abstract

Background: C1q/TNF-related protein 3 (CTRP3) has been clarified to display its protective roles in cardiac function. The current study is concentrated on exploring the impacts of CTRP3 on myocardial ischaemia.

Materials and methods: Oxygen and glucose hypoxia/reoxygenation (OGD/R) model was constructed in human cardiac microvascular endothelial cells (HCMECs). Reverse transcription-quantitative polymerase chain reaction and western blot analysis of CTRP3 expression were conducted. CCK-8 assay was to estimate cell activity and lactate dehydrogenase (LDH) assay kit was to test LDH release. TUNEL assay and western blot were to judge apoptosis. Endothelial barrier function was detected by in vitro vascular permeability assay kit. Zonula occludens-1 (ZO-1) expression was evaluated by immunofluorescence assay. The interaction between CTRP3 promoter and Forkhead Box O6 (FOXO6) was predicted by JASPAR database and verified by chromatin immunoprecipitation and luciferase reporter assays. After OGD/R-induced HCMECs were co-transfected with CTRP3 overexpression and FOXO6 overexpression plasmids, the above functional experiments above were conducted again. Lastly, the expression of sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling-related proteins was examined by western blot.

Results: CTRP3 was down-regulated in OGD/R-induced HCMECs. CTRP3 enhanced the viability and barrier integrity while reduced the apoptosis and permeability of OGD/R-insulted HCMECs. This process may be regulated by FOXO6 transcription. Also, FOXO6 inhibition-mediated CTRP3 up-regulation activated the SIRT1/Nrf2 signalling.

Conclusions: FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling.

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Keywords

myocardial ischaemia, cardiac microvascular endothelial cells, barrier disruption, CTRP3, FOXO6, SIRT1/Nrf2 signalling

About this article
Title

FOXO6 transcription inhibition of CTRP3 promotes OGD/R-triggered cardiac microvascular endothelial barrier disruption via SIRT1/Nrf2 signalling

Journal

Folia Morphologica

Issue

Vol 83, No 1 (2024): Folia Morphologica

Article type

Original article

Pages

125-138

Published online

2023-01-17

Page views

838

Article views/downloads

680

DOI

10.5603/FM.a2023.0002

Pubmed

36688407

Bibliographic record

Folia Morphol 2024;83(1):125-138.

Keywords

myocardial ischaemia
cardiac microvascular endothelial cells
barrier disruption
CTRP3
FOXO6
SIRT1/Nrf2 signalling

Authors

Sanfu Zheng
Yu Wang
Weixi Guo
Hongyu Tan

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