Endothelial Cell Metabolism

Eelen, Guy; Zeeuw, Pauline de; Treps, Lucas; Harjes, Ulrike; Wong, Brian W.; Carmeliet, Peter

doi:10.1152/physrev.00001.2017

Cited by 417 publications

(375 citation statements)

References 651 publications

(746 reference statements)

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“…In the diabetic mouse model with specific knockout of PKC-β, proteinuria was less than that in the control group or in the DKD mice in which proteinuria was alleviated. 23…”

Section: The Inflammatory Response Of Tecs Contributes To the Injurmentioning

confidence: 99%

Crosstalk between tubular epithelial cells and glomerular endothelial cells in diabetic kidney disease

Chen

Liu

et al. 2020

Cell Proliferation

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In recent years, although the development of clinical therapy for diabetic kidney disease (DKD) has made great progress, the progression of DKD still cannot be controlled. Therefore, further study of the pathogenesis of DKD and improvements in DKD treatment are crucial for prognosis. Traditional studies have shown that podocyte injury plays an important role in this process. Recently, it has been found that glomerulotubular balance and tubuloglomerular feedback (TGF) may be involved in the progression of DKD. Glomerulotubular balance is the specific gravity absorption of the glomerular ultrafiltrate by the proximal tubules, which absorbs only 65% to 70% of the ultrafiltrate. This ensures that the urine volume will not change much regardless of whether the glomerular filtration rate (GFR) increases or decreases. TGF is one of the significant mechanisms of renal blood flow and self‐regulation of GFR, but how they participate in the development of DKD in the pathological state and the specific mechanism is not clear. Injury to tubular epithelial cells (TECs) is the key link in DKD. Additionally, injury to glomerular endothelial cells (GECs) plays a key role in the early occurrence and development of DKD. However, TECs and GECs are close to each other in anatomical position and can crosstalk with each other, which may affect the development of DKD. Therefore, the purpose of this review was to summarize the current knowledge on the crosstalk between TECs and GECs in the pathogenesis of DKD and to highlight specific clinical and potential therapeutic strategies.

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“…In the diabetic mouse model with specific knockout of PKC-β, proteinuria was less than that in the control group or in the DKD mice in which proteinuria was alleviated. 23…”

Section: The Inflammatory Response Of Tecs Contributes To the Injurmentioning

confidence: 99%

Crosstalk between tubular epithelial cells and glomerular endothelial cells in diabetic kidney disease

Chen

Liu

et al. 2020

Cell Proliferation

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“…Endothelial cells (EC) rely heavily on glycolysis, with 85% of the ATP requirements coming from the conversion of glucose to lactate [86]. The three EC subsets (tip, stalk and phalanx cells) differ in their metabolic requirements reflective of their individual functions (migration, proliferation and quiescence, respectively).…”

Section: Metabolism Of Synovial Endotheliummentioning

confidence: 99%

Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis

Fearon

Hanlon

Wade

et al. 2018

Clinical and Experimental Immunology

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Rheumatoid arthritis is characterized by synovial proliferation, neovascularization and leucocyte extravasation leading to joint destruction and functional disability. The blood vessels in the inflamed synovium are highly dysregulated, resulting in poor delivery of oxygen; this, along with the increased metabolic demand of infiltrating immune cells and inflamed resident cells, results in the lack of key nutrients at the site of inflammation. In these adverse conditions synovial cells must adapt to generate sufficient energy to support their proliferation and activation status, and thus switch their cell metabolism from a resting regulatory state to a highly metabolically active state. This alters redox-sensitive signalling pathways and also results in the accumulation of metabolic intermediates which, in turn, can act as signalling molecules that further exacerbate the inflammatory response. The RA synovium is a multi-cellular tissue, and while many cell types interact to promote the inflammatory response, their metabolic requirements differ. Thus, understanding the complex interplay between hypoxia-induced signalling pathways, metabolic pathways and the inflammatory response will provide better insight into the underlying mechanisms of disease pathogenesis. OTHER ARTICLES PUBLISHED IN THIS REVIEW SERIESTranslating immunometabolism: towards curing human diseases by targeting metabolic processes underpinning the immune response. Clinical and Experimental Immunology 2019, 197: 141-142. T cell metabolism in chronic viral infection. Clinical and Experimental Immunology 2019, 197: 143-152. Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting. Clinical and Experimental Immunology 2019, 197: 153-160. Sensing between reactions -how the metabolic microenvironment shapes immunity.

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“…Our findings are of broad relevance to the vasculature in the context of other pathophysiologies, including cardiovascular disorders, ocular diseases, diabetes, and brain aneurysms, as well as to normal physiologies exposed to hypoxia (32,33,36,67). Many of these disease states exhibit increased ROS similar to what is observed in hypoxia.…”

Section: Discussionmentioning

confidence: 73%

Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia

Cohen

Geck

Toker

2020

Preprint

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21 The vasculature within a tumor is highly disordered both structurally and functionally. Endothelial 22 cells that comprise the vasculature are poorly connected causing vessels to be leaky and exposing 23 the endothelium to a hypoxic microenvironment. Therefore, most anti-angiogenic therapies are 24 generally inefficient and result in acquired resistance to increased hypoxia due to elimination of 25 the vasculature. Recent studies have explored the efficacy of targeting metabolic pathways in 26 tumor cells in combination with anti-angiogenic therapy. However, the metabolic alterations of 27 endothelial cells in response to hypoxia has been relatively unexplored. Here, we measured polar 28 metabolite levels in microvascular endothelial cells exposed to short-and long-term hypoxia with 29 the goal of identifying metabolic vulnerabilities that can be targeted to normalize tumor 30 vasculature and improve drug delivery. Many amino acid-related metabolites were altered by 31 hypoxia exposure, especially within alanine-aspartate-glutamate, serine-threonine, and cysteine-32 methionine metabolism. Additionally, there were significant changes in de novo pyrimidine 33 synthesis as well as glutathione and taurine metabolism. These results provide key insights into 34 the metabolic alterations that occur in endothelial cells in response to hypoxia, which serve as a 35 foundation for future studies to develop therapies that lead to vessel normalization and more 36 efficient drug delivery. Introduction 38The tumor vasculature is highly disordered with both dense regions of vessels and areas 39 that lack vessels. This leads to inefficient blood flow and delivery of nutrients to a tumor, resulting 40 in a microenvironment that is nutrient-poor and hypoxic (1-3). The endothelial cells that comprise 41 disordered vessels are not tightly connected, resulting in leaky vessels (4,5) and exposing 3 42 endothelial cells to a hypoxic environment. This leakiness also enables tumor cell intravasation 43 and metastasis, and significantly impedes efficient drug delivery to tumors (1,3,6-9). Therefore, a 44 number of therapeutic approaches in cancer treatment have focused on normalizing the disordered 45 tumor vasculature. 46Traditionally, the goal of anti-angiogenic therapies (AATs) was to eradicate the vasculature 47 and deprive tumors of nutrients (10). Many AATs are approved or in clinical trials for treatment 48 of solid tumors as monotherapies or in combination with chemotherapy (9,11-15). However, 49 tumors adapt to the hypoxic microenvironment induced by AATs and develop resistance to therapy 50 (16-22). To overcome these limitations, an alternative approach to targeting the tumor vasculature 51 has been explored, whereby pruning and normalization of the tumor vasculature promotes the 52 highly ordered vasculature found within normal tissues. The resulting increased oxygenation and 53 blood flow in turn allows efficient drug delivery (1,3,23). Normalization of the tumor vasculature 54 has been achieved in several clinical studies f...

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Endothelial Cell Metabolism

Cited by 417 publications

References 651 publications

Crosstalk between tubular epithelial cells and glomerular endothelial cells in diabetic kidney disease

Crosstalk between tubular epithelial cells and glomerular endothelial cells in diabetic kidney disease

Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis

Metabolic pathway alterations in microvascular endothelial cells in response to hypoxia

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