Energetic response of coronary endothelial cells to hypoxia

Mertens, S.; Noll, Thomas; Spahr, R.; Krützfeldt, A.; Piper, Hans Michael

doi:10.1152/ajpheart.1990.258.3.h689

Cited by 84 publications

(80 citation statements)

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“…The lack of oxygen leads to massive changes in the cellular steady state. This was supported by the fact that glucose consumption showed marked changes only after 24h of hypoxia, indicating the change from oxidative phosphorylation to anaerobic glycolysis (20), and resulting in a reduced production of high energy phosphates. The creatine phosphate content reacted more sensitively than ATP, which decreased after longer periods of hypoxia.…”

Section: Discussionmentioning

confidence: 80%

In Vitro Effects of Hypoxia and Reoxygenation on Human Umbilical Endothelial Cells

Windischbauer

Griesmacher²,

Müller³

1994

CCLM

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Summary:We investigated metabolic changes in human umbilical venous endothelial cells, when these were incubated under hypoxic followed by hyperoxic conditions, thus simulating hypoxia and reoxygenation..The human umbilical venous endothelial cells were incubated with a degassed buffer (oxygen content: 0-0.5%) for either 3 h or 24h, followed by a 60min incubation with oxygen-perfused buffer (oxygen content: 100%). Three hours of hypoxia led to a slight decrease in the ATP and creatine phosphate content (-16% ± 5%), while a pronounced decrease of high energy phosphates (-54% ± 4%) was observed after 24 h of hypoxia. Reoxygenating the cells after 3 h of hypoxia led to restoration of the content of high energy phosphates, while reoxygenation after 24 h resulted in a strong decrease (-66% ± 4%). The prostaglandin I 2 release during the first 3 h of hypoxia exceeded the release in the following 21 h. In all cases, reoxygenation increased the prostaglandin I 2 release. Under normoxic conditions the ratio between oxidised glutathione and reduced glutathione shifted from l : 100 to l : 4.5 after 3 h of hypoxia. The content of lipid peroxidation products was almost unaffected during hypoxia, whereas reoxygenation resulted in a pronounced increase (+ 380% ± 60%). The results of this in vitro study suggest that relatively long periods of hypoxia lead to a deficiency of high energy phosphates in the cell. Reoxygenation leads to the formation of oxygen-derived radicals, irrespectively of a prior hypoxia.

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Section: Discussionmentioning

confidence: 80%

In Vitro Effects of Hypoxia and Reoxygenation on Human Umbilical Endothelial Cells

Windischbauer

Griesmacher²,

Müller³

1994

CCLM

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“…In contrast, exposure to longer periods of hypoxia (18 h) modified the uptake and incorporation of radiolabeled adenosine or guanosine in both endothelial cells and renal tubular epithelial cells; however, these alterations were different depending on the cell type (Table I). In PAEC, despite no change in the uptake of either nucleoside after exposure to acute hypoxia for 18 h, incorporation into purine nucleotide phosphates increased twofold in both cases. Thus, the amount of exogenous adenosine or guanosine incorporated into purine nucleotide phosphates was significantly higher in hypoxic PAEC than in their normoxic counterparts.…”

Section: Methodsmentioning

confidence: 79%

“…Although little is known about the mechanisms by which endothelial cells, particularly PAEC, maintain cellular and functional integrity under these physiological and pathological conditions, several recent studies have linked their hypoxia tolerance, in part, to the ability to preserve plasma membrane integrity (16) and to underlying modes of energy metabolism (17)(18)(19). The latter studies have shown that endothelial cells are predominantly governed by glycolytic metabolism and possess a large capacity to increase this metabolism.…”

Section: Introductionmentioning

confidence: 99%

Endothelial cell tolerance to hypoxia. Potential role of purine nucleotide phosphates.

Tret’yakov

Farber²

1995

J. Clin. Invest.

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The ability of cells to tolerate hypoxia is critical to their survival, but varies greatly among different cell types. Despite alterations in many cellular responses during hypoxic exposure, pulmonary arterial endothelial cells (PAEC) retain their viability and cellular integrity. Under similar experimental conditions, other cell types, exemplified by renal tubular epithelial cells, are extremely hypoxia sensitive and are rapidly and irreversibly damaged. To investigate potential mechanisms by which PAEC maintain cellular and functional integrity under these conditions, we compared the turnover of adenine and guanine nucleotides in hypoxia tolerant PAEC and in hypoxia-sensitive renal tubular endothelial cells under various hypoxic conditions. Under several different hypoxic conditions, hypoxia-tolerant PAEC maintained or actually increased ATP levels and the percentage of these nucleotides found in the high energy phosphates, ATP and GTP. In contrast, in hypoxia-sensitive renal tubular endothelial cells, the same high energy phosphates were rapidly depleted. Yet, in both cell types, there were minor alterations in the uptake of the precusor nucleotide and its incorporation into the appropriate purine nucleotide phosphates and marked decreases in ATPase and GTPase activity. This maintenance of high energy phosphates in hypoxic PAEC suggests that there exists tight regulation of ATP and GTP turnover in these cells and that preservation of these nucleotides may contribute to the tolerance of PAEC to acute and chronic hypoxia. (J. Clin. Invest. 1995. 95:738-744.)

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“…Accordingly, glucose availability is not a rate-limiting factor because its concentrations are sufficient in interstitial tissue whereas those of oxygen drop away from blood vessels (Buchwald, 2011;Gatenby and Gillies, 2004). Although lack of glucose enhances endothelial cell vulnerability to hypoxia, when sufficiently high concentrations of glucose are present, glycolysis can generate as much ATP as glucose oxidation because glycolysis rapidly produces ATP (Locasale and Cantley, 2011;Mertens et al, 1990). Rapid ATP production through compartmentalized or local glycolysis also enables endothelial cells to quickly adapt filopodia and lamellipodia during angiogenesis and migration (De Bock et al, 2013b;Lamalice et al, 2007).…”

Section: Etcmentioning

confidence: 99%

Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism

Stapor

Wang

Goveia

et al. 2014

Journal of Cell Science

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Clinically approved therapies that target angiogenesis in tumors and ocular diseases focus on controlling pro-angiogenic growth factors in order to reduce aberrant microvascular growth. Although research on angiogenesis has revealed key mechanisms that regulate tissue vascularization, therapeutic success has been limited owing to insufficient efficacy, refractoriness and tumor resistance. Emerging concepts suggest that, in addition to growth factors, vascular metabolism also regulates angiogenesis and is a viable target for manipulating the microvasculature. Recent studies show that endothelial cells rely on glycolysis for ATP production, and that the key glycolytic regulator 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase 3 (PFKFB3) regulates angiogenesis by controlling the balance of tip versus stalk cells. As endothelial cells acquire a tip cell phenotype, they increase glycolytic production of ATP for sprouting. Furthermore, pharmacological blockade of PFKFB3 causes a transient, partial reduction in glycolysis, and reduces pathological angiogenesis with minimal systemic harm. Although further assessment of endothelial cell metabolism is necessary, these results represent a paradigm shift in anti-angiogenic therapy from targeting angiogenic factors to focusing on vascular metabolism, warranting research on the metabolic pathways that govern angiogenesis.

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Energetic response of coronary endothelial cells to hypoxia

Cited by 84 publications

References 0 publications

In Vitro Effects of Hypoxia and Reoxygenation on Human Umbilical Endothelial Cells

In Vitro Effects of Hypoxia and Reoxygenation on Human Umbilical Endothelial Cells

Endothelial cell tolerance to hypoxia. Potential role of purine nucleotide phosphates.

Angiogenesis revisited – role and therapeutic potential of targeting endothelial metabolism

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