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Autophagy in homocysteine‑induced HUVEC senescence

The senescence of vascular endothelial cells (VECs) drives the occurrence and development of cardiovascular disease (CVD). Homocysteine (HCY) is a general risk factor for age-associated CVDs. Autophagy, an evolutionarily conserved lysosomal protein degradation pathway, serves a part in VEC senescenc...

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Autores principales: Zhang, Yexi, Ouyang, Juyan, Zhan, Liu, Li, Yu, Li, Shaoshan, He, Yi, Wang, Hong, Zhang, Xiangyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265697/
https://www.ncbi.nlm.nih.gov/pubmed/37324509
http://dx.doi.org/10.3892/etm.2023.12053
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author Zhang, Yexi
Ouyang, Juyan
Zhan, Liu
Li, Yu
Li, Shaoshan
He, Yi
Wang, Hong
Zhang, Xiangyang
author_facet Zhang, Yexi
Ouyang, Juyan
Zhan, Liu
Li, Yu
Li, Shaoshan
He, Yi
Wang, Hong
Zhang, Xiangyang
author_sort Zhang, Yexi
collection PubMed
description The senescence of vascular endothelial cells (VECs) drives the occurrence and development of cardiovascular disease (CVD). Homocysteine (HCY) is a general risk factor for age-associated CVDs. Autophagy, an evolutionarily conserved lysosomal protein degradation pathway, serves a part in VEC senescence. The purpose of this study was to investigate the role of autophagy in HCY-induced endothelial cell senescence and explore novel mechanisms and therapeutic approaches for related CVDs. Human umbilical vein endothelial cells (HUVECs) were isolated from fresh umbilical cords of healthy pregnancies. Cell Counting Kit-8, flow cytometry and senescence-associated (SA) β-galactosidase (Gal) staining demonstrated that HCY induced HUVEC senescence by decreasing cell proliferation, arresting cell cycle and increasing the number of SA-β-Gal-positive cells. Stub-RFP-Sens-GFP-LC3 autophagy-related double fluorescence lentivirus revealed that HCY increased autophagic flux. Further, inhibition of autophagy using 3-methyladenine increased HCY-induced HUVEC senescence. By contrast, the induction of autophagy via rapamycin alleviated HCY-induced HUVEC senescence. Finally, the detection of reactive oxygen species (ROS) with ROS kit showed that HCY increased intracellular ROS, whereas induction of autophagy reduced intracellular ROS. In conclusion, HCY increased HUVEC senescence and upregulated autophagy; moderate autophagy could reverse HCY-induced cell senescence. Autophagy may alleviate HCY-induced cell senescence by decreasing intracellular ROS. This provides insight into the underlying mechanism of HCY-induced VEC senescence and potential treatments for age-associated CVDs.
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spelling pubmed-102656972023-06-15 Autophagy in homocysteine‑induced HUVEC senescence Zhang, Yexi Ouyang, Juyan Zhan, Liu Li, Yu Li, Shaoshan He, Yi Wang, Hong Zhang, Xiangyang Exp Ther Med Articles The senescence of vascular endothelial cells (VECs) drives the occurrence and development of cardiovascular disease (CVD). Homocysteine (HCY) is a general risk factor for age-associated CVDs. Autophagy, an evolutionarily conserved lysosomal protein degradation pathway, serves a part in VEC senescence. The purpose of this study was to investigate the role of autophagy in HCY-induced endothelial cell senescence and explore novel mechanisms and therapeutic approaches for related CVDs. Human umbilical vein endothelial cells (HUVECs) were isolated from fresh umbilical cords of healthy pregnancies. Cell Counting Kit-8, flow cytometry and senescence-associated (SA) β-galactosidase (Gal) staining demonstrated that HCY induced HUVEC senescence by decreasing cell proliferation, arresting cell cycle and increasing the number of SA-β-Gal-positive cells. Stub-RFP-Sens-GFP-LC3 autophagy-related double fluorescence lentivirus revealed that HCY increased autophagic flux. Further, inhibition of autophagy using 3-methyladenine increased HCY-induced HUVEC senescence. By contrast, the induction of autophagy via rapamycin alleviated HCY-induced HUVEC senescence. Finally, the detection of reactive oxygen species (ROS) with ROS kit showed that HCY increased intracellular ROS, whereas induction of autophagy reduced intracellular ROS. In conclusion, HCY increased HUVEC senescence and upregulated autophagy; moderate autophagy could reverse HCY-induced cell senescence. Autophagy may alleviate HCY-induced cell senescence by decreasing intracellular ROS. This provides insight into the underlying mechanism of HCY-induced VEC senescence and potential treatments for age-associated CVDs. D.A. Spandidos 2023-05-31 /pmc/articles/PMC10265697/ /pubmed/37324509 http://dx.doi.org/10.3892/etm.2023.12053 Text en Copyright: © Zhang et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhang, Yexi
Ouyang, Juyan
Zhan, Liu
Li, Yu
Li, Shaoshan
He, Yi
Wang, Hong
Zhang, Xiangyang
Autophagy in homocysteine‑induced HUVEC senescence
title Autophagy in homocysteine‑induced HUVEC senescence
title_full Autophagy in homocysteine‑induced HUVEC senescence
title_fullStr Autophagy in homocysteine‑induced HUVEC senescence
title_full_unstemmed Autophagy in homocysteine‑induced HUVEC senescence
title_short Autophagy in homocysteine‑induced HUVEC senescence
title_sort autophagy in homocysteine‑induced huvec senescence
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265697/
https://www.ncbi.nlm.nih.gov/pubmed/37324509
http://dx.doi.org/10.3892/etm.2023.12053
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