What question did this study set out to answer?

To identify the metabolic fuels required for resting platelets and thrombin-induced aggregation, and to evaluate platelet metabolic plasticity under metabolic inhibition.

April 13, 2015PLoS ONEOpen Access

Metabolic Plasticity in Resting and Thrombin Activated Platelets

Q: What is the clinical evidence from this study?

Study design: Other. Population: Healthy (platelet metabolism) (n=9). Intervention: Thrombin and metabolic inhibitors vs. Resting platelets (vehicle/media). Primary outcome: Platelet aggregation and bioenergetics (OCR and ECAR).

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Key result

Thrombin stimulates both glycolysis and oxidative phosphorylation in platelets, and combined inhibition of both pathways synergistically inhibits platelet aggregation.

Why the study?

Does inhibition of specific metabolic pathways (glycolysis, fatty acid oxidation, glutaminolysis) prevent thrombin-dependent platelet aggregation and alter bioenergetics in human platelets?

Population

Platelets isolated from healthy human donors.

Comparison

Thrombin activation in the presence or absence… vs Resting platelets or thrombin-activated…

Design

Preclinical

Authors

SRSaranya RaviNetaji Subhash Chandra Bose Medical College BCBalu K. ChackoUniversity of Alabama at Birmingham HSHirotaka SawadaUniversity of Alabama at Birmingham

Discussion

Member takes

Implication

Metabolic platelet inhibition remains investigational; hypothesis-generating in animals and requires human validation before any clinical consideration.

Key Points

To identify the metabolic fuels required for resting platelets and thrombin-induced aggregation, and to evaluate platelet metabolic plasticity under metabolic inhibition.
Isolated platelets from healthy human donors to evaluate bioenergetics and fuel requirements in resting and thrombin-stimulated conditions.
Inhibited fatty acid oxidation, glutaminolysis, and glycolysis individually and in combination during thrombin-induced platelet aggregation.
Thrombin stimulation triggered a rapid increase in oxidative phosphorylation fueled by fatty acids and glutamine without evidence of mitochondrial dysfunction.
Inhibition of fatty acid oxidation and glutaminolysis alone or combined failed to stop aggregation due to compensatory increases in glycolytic flux.
Inhibitors of glycolysis reduced platelet aggregation by approximately 50%, while combining glycolytic and oxidative phosphorylation inhibitors synergistically suppressed aggregation.

Structured PICO

Does inhibition of specific metabolic pathways (glycolysis, fatty acid oxidation, glutaminolysis) prevent thrombin-dependent platelet aggregation and alter bioenergetics in human platelets?

Population

Platelets isolated from 9 healthy male and female volunteers aged 25-60 years with no chronic diseases.

Intervention

Thrombin activation (0.5 U/ml) in the presence or absence of metabolic inhibitors (etomoxir, trimetazidine, 2-deoxy-D-glucose, koningic acid, antimycin A, azaserine) or specific substrate depletion (glutamine, fatty acids).

Comparator

Resting platelets (vehicle/media) or thrombin-activated platelets without metabolic inhibition.

Outcome

Platelet bioenergetics (oxygen consumption rate [OCR] and extracellular acidification rate [ECAR]) and platelet aggregation.surrogate

Platelets exhibit metabolic plasticity during thrombin activation, relying on both glycolysis and oxidative phosphorylation, with glycolysis able to compensate for the loss of fatty acid oxidation or glutaminolysis to sustain aggregation.

Limitations

In vitro study using isolated platelets
Small sample size of donors (n=9)
Individual variation in basal OCR and ECAR among donors

Cite This Study

Ravi et al. (2015) studied Healthy (platelet metabolism) (n=9). Thrombin and metabolic inhibitors vs. Resting platelets (vehicle/media) was evaluated on Platelet aggregation and bioenergetics (OCR and ECAR). Thrombin stimulates both glycolysis and oxidative phosphorylation in platelets, and combined inhibition of both pathways synergistically inhibits platelet aggregation.

synapsesocial.com/papers/6a1efdbd08df8bb755b30658 https://doi.org/10.1371/journal.pone.0123597

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Implication

Metabolic platelet inhibition remains investigational; hypothesis-generating in animals and requires human validation before any clinical consideration.

Metabolic Plasticity in Resting and Thrombin Activated Platelets

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Metabolic Plasticity in Resting and Thrombin Activated Platelets

Discussion

Member takes

Implication

Key Points

Structured PICO

Limitations

Cite This Study

Also Consider

Also Consider