VEGF Triggers Transient Induction of Autophagy in Endothelial Cells via AMPKα1

Spengler, Katrin; Kryeziu, Nderim; Größe, Silke; Mosig, Alexander S.; Heller, Regine

doi:10.3390/cells9030687

Cited by 34 publications

(29 citation statements)

References 80 publications

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“…Growth of the vascular network is a highly dynamic process, comprising many individual steps promoting the dynamic shift between quiescence and proliferation and sprouting of ECs. Recent research demonstrated that vascular endothelial growth factor (VEGF) activates autophagic flux by an AMPK-dependent mechanism [33]. Notably, the activation of autophagy in response to VEGF is transient, and it is opposed by a delayed activation of mTOR by VEGF itself [33].…”

Section: Autophagy Controls Endothelial Cells Homeostasis and Functionsmentioning

confidence: 99%

Autophagy at the interface of endothelial cell homeostasis and vascular disease

Mameli

Martello²,

Caporali

2021

The FEBS Journal

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Autophagy is an essential intracellular process for cellular quality control. It enables cell homeostasis through the selective degradation of harmful protein aggregates and damaged organelles. Autophagy is essential for recycling nutrients, generating energy to maintain cell viability in most tissues and during adverse conditions such as hypoxia/ischaemia. The progressive understanding of the mechanisms modulating autophagy in the vasculature has recently led numerous studies to link intact autophagic responses with endothelial cell (EC) homeostasis and function. Preserved autophagic flux within the ECs has an essential role in maintaining their physiological characteristics, whereas defective autophagy can promote endothelial pro‐inflammatory and atherogenic phenotype. However, we still lack a good knowledge of the complete molecular repertoire controlling various aspects of endothelial autophagy and how this is associated with vascular diseases. Here, we provide an overview of the current state of the art of autophagy in ECs. We review the discoveries that have so far defined autophagy as an essential mechanism in vascular biology and analyse how autophagy influences ECs behaviour in vascular disease. Finally, we emphasise opportunities for compounds to regulate autophagy in ECs and discuss the challenges of exploiting them to resolve vascular disease.

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Section: Autophagy Controls Endothelial Cells Homeostasis and Functionsmentioning

confidence: 99%

Autophagy at the interface of endothelial cell homeostasis and vascular disease

Mameli

Martello²,

Caporali

2021

The FEBS Journal

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“…HUVEC were isolated from anonymously acquired human umbilical cords according to the "Ethical principles for Medical Research Involving Human Subjects" (Declaration of Helsinki 1964) as previously described (Spengler et al, 2020). The protocol was approved by the Jena University Hospital Ethics Committee.…”

Section: Huvec Cell Culture and Treatmentmentioning

confidence: 99%

Mapping sites of carboxymethyllysine modification on proteins reveals its consequences for proteostasis and cell proliferation

Sanzo

Spengler

Leheis

et al. 2020

Preprint

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Posttranslational mechanisms play a key role in modifying the abundance and function of cellular proteins. Among these, modification by advanced glycation end products (AGEs) has been shown to accumulate during aging and age-associated diseases but specific protein targets and functional consequences remain largely unexplored. Here, we devised a proteomic strategy to identify specific sites of carboxymethyllysine (CML) modification, one of the most abundant AGEs. We identified over 1000 sites of CML modification in mouse and primary human cells treated with the glycating agent glyoxal. By using quantitative proteomics, we found that protein glycation triggers a proteotoxic response and directly affects the protein degradation machinery. We show that glyoxal induces cell cycle perturbation in primary endothelial cells and that CML modification reduces acetylation of tubulins and impairs microtubule dynamics. Our data demonstrate the relevance of AGE modification for cellular function and pinpoint specific protein networks that might become compromised during aging.

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“…For example, Chen et al found that VEGF promoted the occurrence of autophagy and VEGF knockdown decreased the autophagy level 39 . In addition, Spengler et al 40 discovered that VEGF signaling pathway regulated autophagy in endothelial cells. Taken together, we speculated that autophagy probably contributed to the occurrence and development of LUAD through VEGF signaling pathway, and that the ARlncRNA signature was closely associated with tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma

Chen

Sang

et al. 2021

Preprint

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Background: Autophagy is closely associated with the tumor immune microenvironment (TIME) and prognosis of patients with lung adenocarcinoma (LUAD). In the present study, we established a signature based on long noncoding RNAs (lncRNAs) related to autophagy (ARlncRNAs) to investigate the TIME and survival of LUAD patients.Methods: We selected ARlncRNAs associated with prognosis to construct a model, and divided each sample into different groups based on risk score. Subsequently, Kaplan-Meier survival analysis was performed to investigate the survival outcomes of LUAD patients in different group. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis explored the enriched pathways and functions. Several bioinformatics analyses were conducted to explore the TIME of LUAD patients in different group.Results: The ARlncRNAs signature could be recognized as an independent prognostic factor for LUAD patients, and patients in the low-risk group had a greater survival advantage. GO and KEGG enrichment analysis suggested that several immune functions and pathways were enriched in different groups. A high-risk score correlated significantly negatively with high abundance of immune cells and stromal cells around the tumor and high tumor mutational burden (TMB). Low-risk patients had a higher PD-1, CTLA-4 and HAVCR2 expression, and had a better efficacy of immune checkpoint inhibitor (ICIs), including PD-1/CTLA-4 inhibitor.Conclusions: A reliable signature based on ARlncRNAs was constructed to explore the TIME and prognosis of LUAD patients, which could provide valuable information for individualized LUAD treatment.

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VEGF Triggers Transient Induction of Autophagy in Endothelial Cells via AMPKα1

Cited by 34 publications

References 80 publications

Autophagy at the interface of endothelial cell homeostasis and vascular disease

Autophagy at the interface of endothelial cell homeostasis and vascular disease

Mapping sites of carboxymethyllysine modification on proteins reveals its consequences for proteostasis and cell proliferation

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma

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