The Induction of Endothelial Autophagy and Its Role in the Development of Atherosclerosis

Hua, Yunqing; Zhang, Jing; Liu, Qianqian; Su, Jing; Zhao, Yun; Zheng, Guobin; Zhang, Yang; Zhuo, Danping; Ma, Chuanrui; Fan, Guanwei

doi:10.3389/fcvm.2022.831847

Cited by 23 publications

(14 citation statements)

References 140 publications

(155 reference statements)

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“…It is well known that the treatment with native and oxidized low-density lipoproteins, angiostatin, homocysteine and high glucose rates can cause eNOS uncoupling, inducing a state similar to ED ( Incalza et al, 2018 ). Other works induce endothelial dysfunction through the induction of endothelial cell autophagy or through the induction of oxidative stress ( Gupta et al, 2022 ; Hua et al, 2022 ). However, from previous results of our research group in which L-NAME was used for the induction of secondary hypertension in vivo ( Fürstenau et al, 2010 ), we found the need to develop an in vitro model to mimic this condition, especially ED, following a similar method of treatment to study other aspects related to the development and establishment of the disease.…”

Section: Discussionmentioning

confidence: 99%

Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model

et al. 2022

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The vascular endothelium plays a pivotal role in the maintenance of vascular homeostasis, mediated by vasoactive molecules produced by endothelial cells. The balance between vasoconstrictor and vasodilator biomolecules is what guarantees this equilibrium. Therefore, an increase in the bioavailability of vasoconstrictors along with a reduction in vasodilators may indicate a condition known as endothelial dysfunction. Endothelial dysfunction is marked by an inflammatory process and reduced activity of vasoprotective enzymes, being characterized by some factors like the reduction of the bioavailability of nitric oxide (NO) and increase in the production of reactive oxygen species (ROS), pro-inflammatory and vasoconstrictor molecules. This condition is a predictive marker of several cardiovascular diseases (e.g., atherosclerosis, hypertension, and diabetes). Research is affected by the scarcity of suitable in vitro models that simulate endothelial dysfunction. The goal of this study was to induce an in vitro condition to mimic endothelial dysfunction by inhibiting NO synthesis in cells. Thymus-derived endothelial cells (tEnd.1) were treated with different concentrations of L-NAME (from 1 to 1,000 μM) for different times (12, 24, 48, 72, 96, and 120 h without and with retreatment every 24 h). Cell viability, nitrite concentration, p22phox, NOX2, NOX4, IL-6, and ACE genes expression and lipid peroxidation were evaluated. The results indicate that the treatment with 100 μM L-NAME for 72 h without retreatment reduced NO concentration and NOX4 gene expression while increasing ACE expression, thus mimicking reduced vascular protection and possibly increased vasoconstriction. On the other hand, treatment with 100 μM L-NAME for 96 h with retreatment reduced the concentration of NO and the expression of the p22phox gene while increasing the expression of the IL-6 and ACE genes, mimicking the increase in inflammation and vasoconstriction parameters. Based on these results, we thus propose that both 100 μM L-NAME for 72 h without retreatment and 100 μM L-NAME for 96 h with retreatment may be used as models for in vitro endothelial dysfunction according to the purpose of the study to be conducted.

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Section: Discussionmentioning

confidence: 99%

Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model

et al. 2022

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“…Autophagy plays a major role in many diseases, including immune diseases [ 35 , 36 ], neurodegenerative diseases [ 37 ], atherosclerosis [ 38 ], and cancers [ 39 , 40 ]. Our present work suggests that autophagy may also have a role in eosinophilic asthma.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Esnault

Fichtinger

Barretto

et al. 2022

Cells

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The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents.

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“…In recent years, attention has been paid to the role of autophagy in the health of blood vessel walls ( Hua et al, 2022 ). Macroautophagy has proven important in endothelial cells (ECs) ( Torisu et al, 2016 ), vascular smooth muscle cells (VSMCs) ( Grootaert et al, 2015 ) and macrophages ( Ouimet et al, 2011 ) for maintenance of vasculature homeostasis, in response to lipid challenges and protection against atherosclerosis ( Henderson et al, 2021 ).…”

Section: Chaperone-mediated Autophagy In Stem Cellsmentioning

confidence: 99%

Role of Chaperone-Mediated Autophagy in Ageing Biology and Rejuvenation of Stem Cells

Vitale

Perveen

Rossin

et al. 2022

Front. Cell Dev. Biol.

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What lies at the basis of the mechanisms that regulate the maintenance and self-renewal of pluripotent stem cells is still an open question. The control of stemness derives from a fine regulation between transcriptional and metabolic factors. In the last years, an emerging topic has concerned the involvement of Chaperone-Mediated Autophagy (CMA) as a key mechanism in stem cell pluripotency control acting as a bridge between epigenetic, transcriptional and differentiation regulation. This review aims to clarify this new and not yet well-explored horizon discussing the recent studies regarding the CMA impact on embryonic, mesenchymal, and haematopoietic stem cells. The review will discuss how CMA influences embryonic stem cell activity promoting self-renewal or differentiation, its involvement in maintaining haematopoietic stem cell function by increasing their functionality during the normal ageing process and its effects on mesenchymal stem cells, in which modulation of CMA regulates immunosuppressive and differentiation properties. Finally, the importance of these new discoveries and their relevance for regenerative medicine applications, from transplantation to cell rejuvenation, will be addressed.

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The Induction of Endothelial Autophagy and Its Role in the Development of Atherosclerosis

Cited by 23 publications

References 140 publications

Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model

Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Role of Chaperone-Mediated Autophagy in Ageing Biology and Rejuvenation of Stem Cells

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