Lactate, with Oxygen, Incites Angiogenesis

Hunt, Thomas K.; Aslam, Rummana; Hussain, Zamir; Beckert, Stefan

doi:10.1007/978-0-387-74911-2_9

Cited by 55 publications

(47 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A multitude of data demonstrates that increased oxygen levels lead to increased angiogenesis, and the key metabolic component that stimulates this process appears to be lactate [29]. Lactate induces angiogenesis in an oxygen dependent manner, and this can be inhibited by inhibition of lactate dehydrogenase [30].…”

Section: Discussionmentioning

confidence: 99%

“…These cells are responding to a variety of growth factors and cytokines that interact to regulate the process of repair, and this complexity is not recapitulated in the in vitro experiments. Normally, Hif1α protein and VEGF increase when cells are hypoxic, but in the presence of inflammation and lactate, as in wounds, the effects is different, and oxygen promotes VEGF expression and angiogenesis [8, 29–31]. The goal of the current study was to determine the role of oxygen in bone repair in vivo and to explore the efficacy of non-hyperbaric hyperoxia on enhancement of fracture healing.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of oxygen during fracture healing

Saless

Wang

et al. 2013

Bone

Self Cite

View full text Add to dashboard Cite

Oxygen affects the activity of multiple skeletogenic cells and is involved in many processes that are important for fracture healing. However, the role of oxygen in fracture healing has not been fully studied. Here we systematically examine the effects of oxygen tension on fracture healing and test the ability of hyperoxia to rescue healing defects in a mouse model of ischemic fracture healing. Mice with tibia fracture were housed in custom-built gas chambers and groups breathed a constant atmosphere of 13% oxygen (hypoxia), 21% oxygen (normoxia), or 50% oxygen (hyperoxia). The influx of inflammatory cells to the fracture site, stem cell differentiation, tissue vascularization, and fracture healing were analyzed. In addition, the efficacy of hyperoxia (50% breathing oxygen) as a treatment regimen for fracture nonunion was tested. Hypoxic animals had decreased tissue vascularity, decreased bone formation, and delayed callus remodeling. Hyperoxia increased tissue vascularization, altered fracture healing in un-complicated fractures, and improved bone repair in ischemia-induced delayed fracture union. However, neither hypoxia nor hyperoxia significantly altered chondrogenesis or osteogenesis during early stages of fracture healing, and infiltration of macrophages and neutrophils was not affected by environmental oxygen after bone injury. In conclusion, our results indicate that environmental oxygen levels affect tissue vascularization and fracture healing, and that providing oxygen to patients with fractures accompanied by ischemia may be beneficial.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of oxygen during fracture healing

Saless

Wang

et al. 2013

Bone

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lactate accumulation signals the metabolic need to stabilize HIF expression and regulate redox balance, thus facilitating more glycolysis, collagen deposition, and angiogenesis in a positive feedback loop. 47,48 Moreover, it was seen in rat and mouse fibrillar collagen that supplying lactate to the culture activates prolyl hydroxylase proenzyme by suppressing ADP-ribosylation. 46,49,50 Increased lactate production thus induces hydroxylation of proline.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia and Amino Acid Supplementation Synergistically Promote the Osteogenesis of Human Mesenchymal Stem Cells on Silk Protein Scaffolds

Sengupta

Park

Patel

et al. 2010

Tissue Engineering Part A

View full text Add to dashboard Cite

Tailoring tissue engineering strategies to match patient-and tissue-specific bone regeneration needs offers to improve clinical outcomes. As a step toward this goal, osteogenic outcomes and metabolic parameters were assessed when varying inputs into the bone formation process. Silk protein scaffolds seeded with human mesenchymal stem cells in osteogenic differentiation media were used to study in vitro osteogenesis under varied conditions of amino acid (lysine and proline) concentration and oxygen level. The cells were assessed to probe how the microenvironment impacted metabolic pathways and thus osteogenesis. The most favorable osteogenesis outcomes were found in the presence of low (5%) oxygen combined with high lysine and proline concentrations during in vitro cultivation. This same set of culture conditions also showed the highest glucose consumption, lactate synthesis, and certain amino acid consumption rates. On the basis of these results and known pathways, a holistic metabolic model was derived which shows that lysine and proline supplements as well as low (5%) oxygen levels regulate collagen matrix synthesis and thereby rates of osteogenesis. This study establishes early steps toward a foundation for patient-and tissue-specific matches between metabolism, repair site, and tissue engineering approaches toward optimized bone regeneration.

show abstract

“…These inflammatory stimuli also induce VEGF secretion in lung cancer with MPE [9,31]. The product of glycolysis, lactate, has also been proven to incite angiogenesis, even in a normoxic environment [32].…”

Section: Discussionmentioning

confidence: 99%

Malignant pleural effusion cells show aberrant glucose metabolism gene expression

Lin

Chen

Tseng

et al. 2010

European Respiratory Journal

View full text Add to dashboard Cite

Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation.Three tissue sample cohorts, seven from healthy lungs, 18 from stage I-III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative realtime PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy.20 up-or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early-to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretion in vitro and in vivo vascular permeability of cancer cell.Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.

show abstract

Lactate, with Oxygen, Incites Angiogenesis

Cited by 55 publications

References 13 publications

The role of oxygen during fracture healing

The role of oxygen during fracture healing

Hypoxia and Amino Acid Supplementation Synergistically Promote the Osteogenesis of Human Mesenchymal Stem Cells on Silk Protein Scaffolds

Malignant pleural effusion cells show aberrant glucose metabolism gene expression

Contact Info

Product

Resources

About