Angiotensin II-induced overexpression of sirtuin 1 contributes to enhanced expression of Giα proteins and hyperproliferation of vascular smooth muscle cells
Angiotensin II (ANG II) plays an important role in the regulation of various physiological functions including proliferation, hypertrophy of vascular smooth muscle cells (VSMCs) through the overexpression of Giα proteins. Sirtuin 1 (Sirt1), a class III histone deacetylase and epigenetic regulator is implicated in a wide range of cellular functions, including migration and growth of VSMCs and in ANG II-induced hypertension. The present study was undertaken to examine the role of Sirt1 in ANG II-induced overexpression of Giα proteins and hyperproliferation of aortic VSMCs. We show that ANG II treatment of VSMCs increased the expression of Sirt1, which was attenuated by AT1 and AT2 receptor antagonists, losartan, and PD123319, respectively. In addition, the knockdown of Sirt1 by siRNA attenuated ANG II-induced overexpression of Giα-2 and Giα-3 proteins, hyperproliferation of VSMCs and the overexpression of cell cycle proteins, cyclin D1, Cdk4, and phosphorylated retinoblastoma proteins. Furthermore, ANG II-induced increased levels of superoxide anion (O2-) and NADPH oxidase activity and increased phosphorylation of ERK1/2 and Akt that are implicated in enhanced expression of Giα proteins and hyperproliferation of VSMCs were also attenuated to control levels by silencing of Sirt1. In addition, depletion of Sirt1 by siRNA also attenuated ANG II-induced enhanced phosphorylation of platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), and insulin-like growth factor receptor (IGFR) in VSMCs. In summary, our results demonstrate that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated mitogen-activated protein (MAP) kinase/Akt signaling pathway enhances the expression of Giα proteins and cell cycle proteins and results in the hyperproliferation of VSMCs.NEW & NOTEWORTHY ANG II regulates various physiological functions including proliferation of VSMCs through the overexpression of Giα proteins. Sirt1, a class III histone deacetylase, is implicated in several cellular functions, including VSMC growth and ANG II-induced hypertension. We showed for the first time that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated MAP kinase/Akt signaling pathway enhances the levels of Giα and cell cycle proteins resulting in the hyperproliferation of VSMCs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:321 |
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| Enthalten in: |
American journal of physiology. Heart and circulatory physiology - 321(2021), 3 vom: 01. Sept., Seite H496-H508 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hossain, Ekhtear [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.09.2021 Date Revised 24.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1152/ajpheart.00898.2020 |
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| Förderinstitution / Projekttitel: |
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NLM328158291 |
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| 245 | 1 | 0 | |a Angiotensin II-induced overexpression of sirtuin 1 contributes to enhanced expression of Giα proteins and hyperproliferation of vascular smooth muscle cells |
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| 520 | |a Angiotensin II (ANG II) plays an important role in the regulation of various physiological functions including proliferation, hypertrophy of vascular smooth muscle cells (VSMCs) through the overexpression of Giα proteins. Sirtuin 1 (Sirt1), a class III histone deacetylase and epigenetic regulator is implicated in a wide range of cellular functions, including migration and growth of VSMCs and in ANG II-induced hypertension. The present study was undertaken to examine the role of Sirt1 in ANG II-induced overexpression of Giα proteins and hyperproliferation of aortic VSMCs. We show that ANG II treatment of VSMCs increased the expression of Sirt1, which was attenuated by AT1 and AT2 receptor antagonists, losartan, and PD123319, respectively. In addition, the knockdown of Sirt1 by siRNA attenuated ANG II-induced overexpression of Giα-2 and Giα-3 proteins, hyperproliferation of VSMCs and the overexpression of cell cycle proteins, cyclin D1, Cdk4, and phosphorylated retinoblastoma proteins. Furthermore, ANG II-induced increased levels of superoxide anion (O2-) and NADPH oxidase activity and increased phosphorylation of ERK1/2 and Akt that are implicated in enhanced expression of Giα proteins and hyperproliferation of VSMCs were also attenuated to control levels by silencing of Sirt1. In addition, depletion of Sirt1 by siRNA also attenuated ANG II-induced enhanced phosphorylation of platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), and insulin-like growth factor receptor (IGFR) in VSMCs. In summary, our results demonstrate that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated mitogen-activated protein (MAP) kinase/Akt signaling pathway enhances the expression of Giα proteins and cell cycle proteins and results in the hyperproliferation of VSMCs.NEW & NOTEWORTHY ANG II regulates various physiological functions including proliferation of VSMCs through the overexpression of Giα proteins. Sirt1, a class III histone deacetylase, is implicated in several cellular functions, including VSMC growth and ANG II-induced hypertension. We showed for the first time that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated MAP kinase/Akt signaling pathway enhances the levels of Giα and cell cycle proteins resulting in the hyperproliferation of VSMCs | ||
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