Histone Deacetylase SIRT1, Smooth Muscle Cell Function, and Vascular Diseases

Wang, Fang; Chen, Hou-Zao

doi:10.3389/fphar.2020.537519

Cited by 14 publications

(10 citation statements)

References 149 publications

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“…Senescent cells impair essential cellular functions by modifying morphology and gene expression patterns. These alterations provoke maladjusted vascular phenotypes that enhance inflammation, thrombosis, and atherosclerosis and impair vasodilation, angiogenesis, and revascularization which contribute to the advancement of cardiovascular disease [ 19 , 27 , 28 ]. Several studies have found that VSMCs show cell senescence in human and rat AAA tissues and that inhibiting the senescence of VSMCs can inhibit the AAA process.…”

Section: Discussionmentioning

confidence: 99%

EZH2 Regulates ANXA6 Expression via H3K27me3 and Is Involved in Angiotensin II-Induced Vascular Smooth Muscle Cell Senescence

Guo

Zhao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objectives. Abdominal aortic aneurysm (AAA) has a high risk of rupture of the aorta and is one of the leading causes of death in older adults. This study is aimed at confirming the influence and mechanism of the abnormally expressed ANXA6 gene in AAA. Methods. Clinical samples were collected for proteome sequencing to screen for differentially expressed proteins. An Ang II-induced vascular smooth muscle cell (VSMC) aging model as well as an AAA animal model was used. Using RT-qPCR to detect the mRNA levels of EZH2, ANXA6, IK-6, and IL-8 in cells and tissues were assessed. Western blotting and immunohistochemistry staining were used apply for the expression of associated proteins in cells and tissues. SA-β-gal staining, flow cytometry, and DHE staining were used to detect senescent cells and the level of ROS. The cell cycle was assessed by flow cytometry. Arterial pathology was observed by HE staining. The aging of VSMCs in arterial tissue was assessed by coimmunofluorescence for α-SMA and p53. Results. There were 24 differentially expressed proteins in the AAA clinical samples, including 10 upregulated protein and 14 downregulated protein, and the differential expression of ANXA6 was associated with vascular disease. Our study found that ANXA6 was highly expressed and EZH2 was lowly expressed in an Ang II-induced VSMC aging model. Knockdown of ANXA6 or overexpression of EZH2 inhibited Ang II-induced ROS, inhibited cell senescence, decreased Ang II evoked G1 arrest, and increased cells in G2 phase, while overexpression of ANXA6 played the opposite role. Overexpression of EZH2 inhibited ANXA6 expression by increasing H3K27me3 modification at the ANXA6 promoter. Simultaneous overexpression of EZH2 and the protective effect of EZH2 on cell senescence were partially reversed by ANXA6. Similarly, ANXA6 was highly expressed and EZH2 was lowly expressed in an Ang II-induced AAA animal model. Knockdown of ANXA6 and overexpression of EZH2 alleviated Ang II-induced VSMC senescence and inhibited AAA progression, while simultaneous overexpression of EZH2 and ANXA6 partially reversed the protective effect of EZH2 on AAA. Conclusion. EZH2 regulates the ANXA6 promoter H3K27me3 modification, inhibits ANXA6 expression, alleviates Ang II-induced VSMC senescence, and inhibits AAA progression.

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Section: Discussionmentioning

confidence: 99%

EZH2 Regulates ANXA6 Expression via H3K27me3 and Is Involved in Angiotensin II-Induced Vascular Smooth Muscle Cell Senescence

Guo

Zhao

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Mammalian sirtuin 1 and sirtuin 3 are the two cores that control metabolic processes and are located in the nucleus and mitochondria, respectively 59 . Changes in the function of SIRT1 and SIRT3 significantly affect the vascular function associated with hypertension 60,61 . AMPK‐SIRT1/3 inhibition can lead to mitochondrial damage followed by mitochondrial oxidative stress caused by SOD2 inactivation.…”

Section: Discussionmentioning

confidence: 99%

Effects of different intensities of continuous training on vascular inflammation and oxidative stress in spontaneously hypertensive rats

Luo

Cao

Niebauer

et al. 2021

J Cellular Molecular Medi

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We aimed to study the effects and underlying mechanism of different intensities of continuous training (CT) on vascular inflammation and oxidative stress in spontaneously hypertensive rats (SHR). Rats were divided into five groups (n = 12): Wistar‐Kyoto rats sedentary group (WKY‐S), sedentary group (SHR‐S), low‐intensity CT group (SHR‐L), medium‐intensity CT group (SHR‐M) and high‐intensity CT group (SHR‐H). Changes in body mass, heart rate and blood pressure were recorded. The rats were euthanized after 14 weeks, and blood and vascular tissue samples were collected. Haematoxylin and Eosin staining was used to observe the aortic morphology, and Western blot was used to detect the expression of mesenteric artery proteins. After CT, the mean arterial pressures improved in SHR‐L and SHR‐M and increased in SHR‐H compared with those in SHR‐S. Vascular inflammation and oxidative stress levels significantly subsided in SHR‐L and SHR‐M (p < 0.05), whereas in SHR‐H, only vascular inflammation significantly subsided (p < 0.05), and oxidative stress remained unchanged (p > 0.05). AMPK and SIRT1/3 expressions in SHR‐L and SHR‐M were significantly up‐regulated than those in SHR‐S (p < 0.05). These results indicated that low‐ and medium‐intensity CT can effectively reduce the inflammatory response and oxidative stress of SHR vascular tissue, and high‐intensity CT can improve vascular tissue inflammation but not oxidative stress.

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“…Epidemiology shows that 1.3% of all deaths in men between the ages of 65 and 85 in developed countries are caused by AAA 2 . The pathology of AAA is characterized by degradation of the extracellular matrix, oxidative stress, vascular inflammation, and senescence of vascular smooth muscle cells [1][2][3][4]. Because the pathogenesis of AAA is elusive, the treatment of AAA currently relies on surgical repair, and no effective drug therapy is available.…”

Section: Introductionmentioning

confidence: 99%

Trimethylamine N-Oxide Promotes Abdominal Aortic Aneurysm Formation by Aggravating Aortic Smooth Muscle Cell Senescence in Mice

Shen

et al. 2022

J. of Cardiovasc. Trans. Res.

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Trimethylamine N-oxide (TMAO) has been linked to cardiovascular disease morbidity and mortality. However, the role of TMAO in the development of abdominal aortic aneurysms (AAAs) is not known. This study investigated the association between TMAO and AAA formation. TMAO and saline were added to the drinking water of angiotensin II (AngII)- and calcium chloride (CaCl2)-induced AAA model mice, respectively. After 4 weeks, the effects of TMAO on AAA development were determined by histology and immunohistology of aortic tissue. The in vitro effects of TMAO were also examined in mouse aortic smooth muscle cells (SMCs). The maximal aortic diameter, incidence of AAA, and degree of elastin degradation were significantly increased in TMAO-treated mice. TMAO also increased the accumulation of the senescence markers p21 and p16, as well as of reactive oxygen species (ROS), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9) in vivo and in vitro. TMAO promoted AAA development in mouse AAA models induced by AngII and CaCl2 by a mechanism involving cellular senescence. Graphical abstract

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Histone Deacetylase SIRT1, Smooth Muscle Cell Function, and Vascular Diseases

Cited by 14 publications

References 149 publications

EZH2 Regulates ANXA6 Expression via H3K27me3 and Is Involved in Angiotensin II-Induced Vascular Smooth Muscle Cell Senescence

EZH2 Regulates ANXA6 Expression via H3K27me3 and Is Involved in Angiotensin II-Induced Vascular Smooth Muscle Cell Senescence

Effects of different intensities of continuous training on vascular inflammation and oxidative stress in spontaneously hypertensive rats

Trimethylamine N-Oxide Promotes Abdominal Aortic Aneurysm Formation by Aggravating Aortic Smooth Muscle Cell Senescence in Mice

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