Angiogenic Factor With G Patch and FHA Domains 1 Is a Novel Regulator of Vascular Injury

Zhou, Boru; Zeng, Sheng; Li, Nan; Yu, Liming; Yang, Guang; Yang, Yuyu; Zhang, Xinjian; Fang, Mingming; Xia, Jun; Xu, Yong

doi:10.1161/atvbaha.117.308992

Cited by 21 publications

(16 citation statements)

References 28 publications

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“…Histone deacetylase enzymes regulate diverse biological function, including gene expression, rendering them potential targets for intervention in a number of diseases (Moreno-Yruela et al, 2018). Among the human zinc-dependent histone deacetylase enzymes, the most recently discovered member, HDAC11, has been shown to play a role in CVDs through promoting apoptosis, oxidative stress and inflammation (Zhou et al, 2017;Fan et al, 2018). A study showed that peritoneal injection of a small-molecule HDAC11 inhibitor significantly attenuated the formation of neointima after carotid artery ligation in Sprague-Dawley rats (Fan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Hydroxytyrosol Acetate Inhibits Vascular Endothelial Cell Pyroptosis via the HDAC11 Signaling Pathway in Atherosclerosis

Yao

Zhang

et al. 2021

Front. Pharmacol.

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Hydroxytyrosol acetate (HT-AC), a natural polyphenolic compound in olive oil, exerts an anti-inflammatory effect in cardiovascular diseases (CVDs). Pyroptosis is a newly discovered form of programmed inflammatory cell death and is suggested to be involved in the atherosclerosis (AS) process. However, the effect of HT-AC on vascular endothelial cell pyroptosis remains unknown. Thus, we aimed to investigate the effect of HT-AC on vascular endothelial cell pyroptosis in AS and related signaling pathways. In vivo studies showed that HT-AC alleviated the formation of atherosclerotic lesions and inhibited pyroptosis in the aortic intima of ApoE−/− mice fed a high-fat diet (HFD) for 12 weeks. In vitro, we found that HT-AC treatment of human umbilical vein endothelial cells (HUVECs) alleviated tumor necrosis factor-alpha (TNF-α)-induced pyroptosis by decreasing the number of PI positive cells, decreasing the enhanced protein expressions of activated caspase-1 and gasdermin D (GSDMD), as well as by decreasing the release of pro-inflammatory interleukin (IL)-1β and IL-6. Besides, HT-AC down-regulated HDAC11 expression in the aortic intima of HFD-fed ApoE−/− mice and TNF-α-stimulated HUVECs. To determine the underlying mechanism of action, molecular docking and drug affinity responsive target stability (DARTS) were utilized to identify whether HDAC11 protein is a target of HT-AC. The molecular docking result showed good compatibility between HT-AC and HDAC11. DARTS study's result showed that HDAC11 protein may be a target of HT-AC. Further study demonstrated that knockdown of HDAC11 augmented the inhibition of HT-AC on pyroptosis in TNF-α-stimulated HUVECs. These findings indicate that HT-AC might prevent vascular endothelial pyroptosis through down-regulation of HDAC11 related signaling pathway in AS.

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Section: Discussionmentioning

confidence: 99%

“…Another study demonstrated that HDAC11 compromised the vascular endothelial barrier function by suppressing the expression of Ve-cadherin (Zhang and Ge, 2017). Besides, it has been reported that treatment of the HDAC11 inhibitor attenuated vascular injury in mice (Zhou et al, 2017). These studies suggested that HDAC11 was involved in CVDs.…”

Section: Introductionmentioning

confidence: 94%

Hydroxytyrosol Acetate Inhibits Vascular Endothelial Cell Pyroptosis via the HDAC11 Signaling Pathway in Atherosclerosis

Yao

Zhang

et al. 2021

Front. Pharmacol.

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“…However, this result was different from the previous findings in mice model of carotid artery injury. After carotid artery injury in mice, Aggf1 expression was decreased in the carotid arteries [ 31 , 32 ]. We supposed that such discrepancy may be due to the difference in animal models and tissue types.…”

Section: Discussionmentioning

confidence: 99%

Aggf1 attenuates neuroinflammation and BBB disruption via PI3K/Akt/NF-κB pathway after subarachnoid hemorrhage in rats

Zhu

Enkhjargal

Huang

et al. 2018

J Neuroinflammation

128

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BackgroundNeuroinflammation and blood-brain barrier (BBB) disruption are two critical mechanisms of subarachnoid hemorrhage (SAH)-induced brain injury, which are closely related to patient prognosis. Recently, angiogenic factor with G-patch and FHA domain 1 (Aggf1) was shown to inhibit inflammatory effect and preserve vascular integrity in non-nervous system diseases. This study aimed to determine whether Aggf1 could attenuate neuroinflammation and preserve BBB integrity after experimental SAH, as well as the underlying mechanisms of its protective roles.MethodsTwo hundred forty-nine male Sprague-Dawley rats were subjected to the endovascular perforation model of SAH. Recombinant human Aggf1 (rh-Aggf1) was administered intravenously via tail vein injection at 1 h after SAH induction. To investigate the underlying neuroprotection mechanism, Aggf1 small interfering RNA (Aggf1 siRNA) and PI3K-specific inhibitor LY294002 were administered through intracerebroventricular (i.c.v.) before SAH induction. SAH grade, neurological score, brain water content, BBB permeability, Western blot, and immunohistochemistry were performed.ResultsExpression of endogenous Aggf1 was markedly increased after SAH. Aggf1 was primarily expressed in endothelial cells and astrocytes, as well as microglia after SAH. Administration of rh-Aggf1 significantly reduced brain water content and BBB permeability, decreased the numbers of infiltrating neutrophils, and activated microglia in the ipsilateral cerebral cortex following SAH. Furthermore, rh-Aggf1 treatment improved both short- and long-term neurological functions after SAH. Meanwhile, exogenous rh-Aggf1 significantly increased the expression of PI3K, p-Akt, VE-cadherin, Occludin, and Claudin-5, as well as decreased the expression of p-NF-κB p65, albumin, myeloperoxidase (MPO), TNF-α, and IL-1β. Conversely, knockdown of endogenous Aggf1 aggravated BBB breakdown, inflammatory response and neurological impairments at 24 h after SAH. Additionally, the protective roles of rh-Aggf1 were abolished by LY294002.ConclusionsTaken together, exogenous Aggf1 treatment attenuated neuroinflammation and BBB disruption, improved neurological deficits after SAH in rats, at least in part through the PI3K/Akt/NF-κB pathway.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1211-8) contains supplementary material, which is available to authorized users.

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“…During the preparation of this article, Zhou et al 65 reported that overexpression of AGGF1 using adenoviruses inhibited neointimal formation induced by carotid artery ligation. However, there are several major differences between our study and that by Zhou et al First, we presented the data on neointimal formation from AGGF1 +/À KO mice, but the Zhou et al study did not have such data.…”

Section: Discussionmentioning

confidence: 99%

Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury

Yao

et al. 2017

JAHA

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BackgroundDespite recent improvements in angioplasty and placement of drug‐eluting stents in treatment of atherosclerosis, restenosis and in‐stent thrombosis impede treatment efficacy and cause numerous deaths. Research efforts are needed to identify new molecular targets for blocking restenosis. We aim to establish angiogenic factor AGGF1 (angiogenic factor with G patch and FHA domains 1) as a novel target for blocking neointimal formation and restenosis after vascular injury.Methods and Results AGGF1 shows strong expression in carotid arteries; however, its expression is markedly decreased in arteries after vascular injury. AGGF1+/− mice show increased neointimal formation accompanied with increased proliferation of vascular smooth muscle cells (VSMCs) in carotid arteries after vascular injury. Importantly, AGGF1 protein therapy blocks neointimal formation after vascular injury by inhibiting the proliferation and promoting phenotypic switching of VSMCs to the contractile phenotype in mice in vivo. In vitro, AGGF1 significantly inhibits VSMCs proliferation and decreases the cell numbers at the S phase. AGGF1 also blocks platelet‐derived growth factor‐BB–induced proliferation, migration of VSMCs, increases expression of cyclin D, and decreases expression of p21 and p27. AGGF1 inhibits phenotypic switching of VSMCs to the synthetic phenotype by countering the inhibitory effect of platelet‐derived growth factor‐BB on SRF expression and the formation of the myocardin/SRF/CArG‐box complex involved in activation of VSMCs markers. Finally, we show that AGGF1 inhibits platelet‐derived growth factor‐BB–induced phosphorylation of MEK1/2, ERK1/2, and Elk phosphorylation involved in the phenotypic switching of VSMCs, and that overexpression of Elk abolishes the effect of AGGF1.Conclusions AGGF1 protein therapy is effective in blocking neointimal formation after vascular injury by regulating a novel AGGF1‐MEK1/2‐ERK1/2‐Elk‐myocardin‐SRF/p27 signaling pathway.

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Angiogenic Factor With G Patch and FHA Domains 1 Is a Novel Regulator of Vascular Injury

Cited by 21 publications

References 28 publications

Hydroxytyrosol Acetate Inhibits Vascular Endothelial Cell Pyroptosis via the HDAC11 Signaling Pathway in Atherosclerosis

Hydroxytyrosol Acetate Inhibits Vascular Endothelial Cell Pyroptosis via the HDAC11 Signaling Pathway in Atherosclerosis

Aggf1 attenuates neuroinflammation and BBB disruption via PI3K/Akt/NF-κB pathway after subarachnoid hemorrhage in rats

Targeting AGGF1 (angiogenic factor with G patch and FHA domains 1) for Blocking Neointimal Formation After Vascular Injury

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