Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling
<p dir="ltr">Hypertension 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)....
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2020
|
| الموضوعات: | |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| _version_ | 1864513563305967616 |
|---|---|
| author | Crystal M. Ghantous (14571292) |
| author2 | Rima Farhat (13738615) Laiche Djouhri (112613) Sarah Alashmar (14571295) Gulsen Anlar (14571300) Hesham M. Korashy (14151747) Abdelali Agouni (14152272) Asad Zeidan (14571310) |
| author2_role | author author author author author author author |
| author_facet | Crystal M. Ghantous (14571292) Rima Farhat (13738615) Laiche Djouhri (112613) Sarah Alashmar (14571295) Gulsen Anlar (14571300) Hesham M. Korashy (14151747) Abdelali Agouni (14152272) Asad Zeidan (14571310) |
| author_role | author |
| dc.creator.none.fl_str_mv | Crystal M. Ghantous (14571292) Rima Farhat (13738615) Laiche Djouhri (112613) Sarah Alashmar (14571295) Gulsen Anlar (14571300) Hesham M. Korashy (14151747) Abdelali Agouni (14152272) Asad Zeidan (14571310) |
| dc.date.none.fl_str_mv | 2020-05-21T21:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1155/2020/6425782 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Molecular_Mechanisms_of_Adiponectin-Induced_Attenuation_of_Mechanical_Stretch-Mediated_Vascular_Remodeling/22015298 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Cell Biology Aging General Medicine Biochemistry |
| dc.title.none.fl_str_mv | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Hypertension 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 10 <i>μ</i>g/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 T-cadherin 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 [<sup>3</sup>H]-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, p-AMPK, 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 (3.1 nM) 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.</p><h2>Other information</h2><p dir="ltr">Published in: Oxidative Medicine and Cellular Longevity<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1155/2020/6425782" target="_blank">http://dx.doi.org/10.1155/2020/6425782</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_dbf47aeaf4e32e3e1aae90790fc924f9 |
| identifier_str_mv | 10.1155/2020/6425782 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22015298 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular RemodelingCrystal M. Ghantous (14571292)Rima Farhat (13738615)Laiche Djouhri (112613)Sarah Alashmar (14571295)Gulsen Anlar (14571300)Hesham M. Korashy (14151747)Abdelali Agouni (14152272)Asad Zeidan (14571310)Biological sciencesBiochemistry and cell biologyCell BiologyAgingGeneral MedicineBiochemistry<p dir="ltr">Hypertension 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 10 <i>μ</i>g/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 T-cadherin 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 [<sup>3</sup>H]-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, p-AMPK, 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 (3.1 nM) 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.</p><h2>Other information</h2><p dir="ltr">Published in: Oxidative Medicine and Cellular Longevity<br>License: <a href="http://creativecommons.org/licenses/by/4.0" target="_blank">http://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1155/2020/6425782" target="_blank">http://dx.doi.org/10.1155/2020/6425782</a></p>2020-05-21T21:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1155/2020/6425782https://figshare.com/articles/journal_contribution/Molecular_Mechanisms_of_Adiponectin-Induced_Attenuation_of_Mechanical_Stretch-Mediated_Vascular_Remodeling/22015298CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/220152982020-05-21T21:00:00Z |
| spellingShingle | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling Crystal M. Ghantous (14571292) Biological sciences Biochemistry and cell biology Cell Biology Aging General Medicine Biochemistry |
| status_str | publishedVersion |
| title | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling |
| title_full | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling |
| title_fullStr | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling |
| title_full_unstemmed | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling |
| title_short | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling |
| title_sort | Molecular Mechanisms of Adiponectin-Induced Attenuation of Mechanical Stretch-Mediated Vascular Remodeling |
| topic | Biological sciences Biochemistry and cell biology Cell Biology Aging General Medicine Biochemistry |