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AuthorGhantous, Crystal M.
AuthorFarhat, Rima
AuthorDjouhri, Laiche
AuthorAlashmar, Sarah
AuthorAnlar, Gulsen
AuthorKorashy, Hesham M.
AuthorAgouni, Abdelali
AuthorZeidan, Asad
Available date2020-05-31T05:34:53Z
Publication Date2020-05-21
Publication NameOxidative Medicine and Cellular Longevityen_US
Identifierhttp://dx.doi.org/10.1155/2020/6425782
CitationGhantous, Crystal & Farhat, Rima & Djouhri, Laiche & Alashmar, Sarah & Anlar, Gulsen & Korashy, Hesham & Agouni, Abdelali & Zeidan, Asad. (2020). Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling. Oxidative Medicine and Cellular Longevity. 2020. 1-15. 10.1155/2020/6425782.
ISSN1942-0900
URIhttp://hdl.handle.net/10576/14980
AbstractHypertension induces vascular hypertrophy, which changes blood vessels structurally and functionally, leading to reduced tissue perfusion and further hypertension. It is also associated with dysregulated levels of the circulating adipokines leptin and adiponectin (APN). Leptin is an obesity-associated hormone that promotes vascular smooth muscle cell (VSMC) hypertrophy. APN is a cardioprotective hormone that has been shown to attenuate hypertrophic cardiomyopathy. In this study, we investigated the molecular mechanisms of hypertension-induced VSMC remodeling and the involvement of leptin and APN in this process. To mimic hypertension, the rat portal vein (RPV) was mechanically stretched, and the protective effects of APN on mechanical stretch-induced vascular remodeling and the molecular mechanisms involved were examined by using 10μg/ml APN. Mechanically stretching the RPV significantly decreased APN protein expression after 24 hours and APN mRNA expression in a time-dependent manner in VSMCs. The mRNA expression of the APN receptors AdipoR1, AdipoR2, and Tcadherin significantly increased after 15 hours of stretch. The ratio of APN/leptin expression in VSMCs significantly decreased after 24 hours of mechanical stretch. Stretching the RPV for 3 days increased the weight and [3H]-leucine incorporation significantly, whereas APN significantly reduced hypertrophy in mechanically stretched vessels. Stretching the RPV for 10 minutes significantly decreased phosphorylation of LKB1, AMPK, and eNOS, while APN significantly increased p-LKB1, pAMPK, and p-eNOS in stretched vessels. Mechanical stretch significantly increased p-ERK1/2 after 10 minutes, whereas APN significantly reduced stretch-induced ERK1/2 phosphorylation. Stretching the RPV also significantly increased ROS generation after 1 hour, whereas APN significantly decreased mechanical stretch-induced ROS production. Exogenous leptin (3.1nM) markedly increased GATA-4 nuclear translocation in VSMCs, whereas APN significantly attenuated leptin-induced GATA-4 nuclear translocation. Our results decipher molecular mechanisms of APN-induced attenuation of mechanical stretch-mediated vascular hypertrophy, with the promising potential of ultimately translating this protective hormone into the clinic.
SponsorThis work was supported by the Medical Practice Plan (MPP), Faculty of Medicine at AUB to AZ, the National Council for Scientific Research of Lebanon (CNRS-L) to CMG, and the graduate teaching/research assistantship support from Qatar University to SA. The publication of this article was funded by the Qatar National Library.
Languageen
Publisherhindawi
SubjectHypertension
Subjectleptin
Subjectadiponectin
TitleMolecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling
TypeArticle
Volume Number2020
ESSN1942-0994


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