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AuthorOla, El Atab
AuthorGhantous, Crystal M.
AuthorEl-Zein, Nabil
AuthorFarhat, Rima
AuthorAgouni, Abdelali
AuthorKorashy, Hesham M.
AuthorDjouhri, Laiche
AuthorKamareddine, Layla
AuthorZibara, Kazem
AuthorZeidan, Asad
Available date2022-01-17T08:31:54Z
Publication Date2021-12-24
Publication NameEuropean Journal of Pharmacology
Identifierhttp://dx.doi.org/10.1016/j.ejphar.2021.174701
CitationOla El Atab, Crystal M. Ghantous, Nabil El-Zein, Rima Farhat, Abdelali Agouni, Hesham M. Korashy, Laiche Djouhri, Layla Kamareddine, Kazem Zibara, Asad Zeidan, Involvement of caveolae in hyperglycemia-induced changes in adiponectin and leptin expressions in vascular smooth muscle cells, European Journal of Pharmacology, 2021, 174701, ISSN 0014-2999, https://doi.org/10.1016/j.ejphar.2021.174701.
ISSN00142999
URIhttps://www.sciencedirect.com/science/article/pii/S0014299921008578?v=s5
URIhttp://hdl.handle.net/10576/25671
AbstractHyperglycemia exerts various harmful effects on the vasculature. Studies have shown an association between the levels of the adipokines leptin and adiponectin (APN) and vascular complications in diabetes mellitus. The aim of our study was to investigate the molecular mechanisms mediated by APN and leptin that are involved in hyperglycemia-induced vascular remodeling, especially at the level of oxidative stress and actin cytoskeleton dynamics. Rat aorta organ culture was used to investigate the effect of hyperglycemia on APN and leptin protein expression in vascular smooth muscle cells (VSMCs) using Western blot analysis and immunohistochemistry. Hyperglycemia lead to a significant increase in APN synthesis in VSMCs, mainly through caveolae, but this increase failed to provide vascular protection because of the decreased expression of APN receptors, especially AdipoR2, which was assessed by qPCR. In addition, hyperglycemia significantly upregulated leptin expression in VSMCs through caveolae and the RhoA/ROCK pathway. These variations lead to a marked increase in reactive oxygen species (ROS) production, detected by dihydroethidium (DHE) staining, and in NADPH oxidase type 4 (Nox4) expression. Moreover, Nox4 mediated the synthesis of APN in hyperglycemia in VSMCs. Finally, hyperglycemia activated the RhoA/ROCK pathway and subsequently induced the polymerization of globular actin (G-actin) into filamentous actin (F-actin), decreasing the G/F-actin ratio. Taken together, these data show that hyperglycemia increases oxidative stress and changes actin cytoskeleton dynamics in the aorta via caveolae, favoring vascular remodeling.
Languageen
PublisherElsevier
SubjectHyperglycemia
Caveolae
Cyclophilin A
Leptin
Adiponectin
Vascular smooth muscle remodeling
TitleInvolvement of caveolae in hyperglycemia-induced changes in adiponectin and leptin expressions in vascular smooth muscle cells
TypeArticle
dc.accessType Abstract Only


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