Overexpression of sFlt-1 represses ox-LDL-induced injury of HUVECs by activating autophagy via PI3K/AKT/mTOR pathway

Zhou, Yihua; Tang, Yuyan; Guo, Liangyun; Zheng, Lili; Zhang, Dan; Yang, Canying; Wang, Wei

doi:10.1016/j.mvr.2021.104252

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…Ang II is the main cause of endothelial cell injury caused by hypertension. Previous studies have suggested that autophagy plays an important role in endothelial cell protection [ 15 ]. Therefore, we first evaluated the effect of Ang II on endothelial autophagy.…”

Section: Resultsmentioning

confidence: 99%

Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo

et al. 2022

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We previously reported that ibandronate (IBAN) could improve endothelial function in spontaneously hypertensive rats. However, the mechanism by which IBAN improves endothelial function is unclear. The IBAN-induced autophagic process in vitro experiments were determined by detection of LC3, Beclin1, and P62 protein levels via western blotting. The autophagy flux was detected by confocal microscopy and transmission electron microscopy. For in vivo experiments, spontaneously hypertensive rats were orally administered with IBAN. Utilizing angiotensin II (Ang II) to stimulate the human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) as a model of endothelial cell injury in hypertension, we found that IBAN promoted autophagy and protected cell viability in Ang II-treated-endothelial cells while these effects could be reversed by autophagy inhibitor. In terms of mechanism, IBAN treatment decreased the levels of Rac1 and mammalian target of rapamycin (mTOR) pathway. Activating either Rac1 or mTOR could reverse IBAN-induced autophagy. Furthermore, the in vivo experiments also indicated that IBAN promotes autophagy by downregulating Rac1-mTOR. Taken together, our results firstly revealed that IBAN enhances autophagy via inhibiting Rac1-mTOR signaling pathway, and thus alleviates Ang II-induced injury in endothelial cells.

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Section: Resultsmentioning

confidence: 99%

Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo

et al. 2022

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“…Emerging evidence has demonstrated that ox-LDL may induce autophagy dysfunction in ECs [ 45 ], while impaired autophagy flux contributes to vascular endothelial dysfunction and atherosclerotic plaque development by regulating lipid metabolism dysfunction [ 19 , 46 ]. Our study confirms autophagic flux impairment and EndMT induced by ox-LDL in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation

Diao

Lan

et al. 2022

Genes

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Atherosclerosis is a chronic systemic inflammatory disease that causes severe cardiovascular events. B cell lymphoma 2-associated athanogene (BAG3) was proven to participate in the regulation of tumor angiogenesis, neurodegenerative diseases, and cardiac diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the role of BAG3 in atherosclerosis and elucidate the potential molecular mechanism. In this study, ApoE−/− mice were given a tail-vein injection of BAG3-overexpressing lentivirus and fed a 12-week high-fat diet (HFD) to investigate the role of BAG3 in atherosclerosis. The overexpression of BAG3 reduced plaque areas and improved atherosclerosis in ApoE−/− mice. Our research proves that BAG3 promotes autophagy in vitro, contributing to the suppression of EndMT in human umbilical vein endothelial cells (HUVECs). Mechanically, autophagy activation is mediated by BAG3 via the interaction between BAG3 and its chaperones HSP70 and HSPB8. In conclusion, BAG3 facilitates autophagy activation via the formation of the chaperone-assisted selective autophagy (CASA) complex interacting with HSP70 and HSPB8, leading to the inhibition of EndMT during the progression of atherosclerosis and indicating that BAG3 is a potential therapeutic target for atherosclerosis.

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“…However, there is also a certain amount of evidence to support the protective effect of activated autophagy on PH. For example, although ox-LDL treatment significantly increases the autophagic flux (LC3-II/LC3-I and Beclin-1) in vascular ECs, inhibition of the PI3K/AKT/mTOR pathway and activation of autophagy by sFlt-1 effectively alleviate ox-LDL-induced apoptosis and cell damage [ 92 ].…”

Section: Autophagymentioning

confidence: 99%

Molecular regulation and therapeutic implications of cell death in pulmonary hypertension

et al. 2023

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Pulmonary hypertension (PH) is a clinical and pathophysiological syndrome caused by changes in pulmonary vascular structure or function that results in increased pulmonary vascular resistance and pulmonary arterial pressure, and it is characterized by pulmonary endothelial dysfunction, pulmonary artery media thickening, pulmonary vascular remodeling, and right ventricular hypertrophy, all of which are driven by an imbalance between the growth and death of pulmonary vascular cells. Programmed cell death (PCD), different from cell necrosis, is an active cellular death mechanism that is activated in response to both internal and external factors and is precisely regulated by cells. More than a dozen PCD modes have been identified, among which apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, and cuproptosis have been proven to be involved in the pathophysiology of PH to varying degrees. This article provides a summary of the regulatory patterns of different PCD modes and their potential effects on PH. Additionally, it describes the current understanding of this complex and interconnected process and analyzes the therapeutic potential of targeting specific PCD modes as molecular targets.

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Overexpression of sFlt-1 represses ox-LDL-induced injury of HUVECs by activating autophagy via PI3K/AKT/mTOR pathway

Cited by 6 publications

References 20 publications

Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo

Ibandronate promotes autophagy by inhibiting Rac1–mTOR signaling pathway in vitro and in vivo

BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation

Molecular regulation and therapeutic implications of cell death in pulmonary hypertension

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