Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity

Nguyen, Quyen Le; Corey, Catherine; White, Pamela; Watson, Annie; Gladwin, Mark T.; Simon, Marc A.; Shiva, Sruti

doi:10.1172/jci.insight.91415

Cited by 50 publications

(57 citation statements)

References 54 publications

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“…In addition to complex activity levels, the source of substrate and availability govern maximal respiration. For example, we have previously shown that in subjects with pulmonary arterial hypertension, maximal respiratory capacity is increased despite no change in the majority of the electron transport complexes, and this was due to a substrate switch from glucose to fatty acid oxidation (20). A limitation of the current study is that we did not measure substrate utility or availability in the platelets.…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 81%

“…Recent studies have demonstrated that mitochondrial function in circulating blood cells can reflect tissue mitochondrial energetics (15)(16)(17). Further, mitochondrial function in circulating platelets and peripheral blood mononuclear cells (PBMCs) correlates with some clinical parameters and physical function, respectively (15,(18)(19)(20)(21)(22). However, it is unclear whether platelets directly reflect mitochondrial function measured in the muscle of older human adults and whether there are measurable changes in platelet bioenergetics in young versus older adults.…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

“…Platelet isolation. Platelets were isolated from peripheral blood samples obtained by standard venipuncture without a tourniquet, to avoid platelet activation as previously described (18,20). Briefly, prostaglandin I 2 (1 μg/mL) was added to whole blood (to further prevent artifactual activation) before it was centrifuged (150 g, 10 minutes) to isolate platelet-rich plasma.…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

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Platelet bioenergetics correlate with muscle energetics and are altered in older adults

Braganza¹,

Corey²,

Santanasto³

et al. 2019

JCI Insight

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P-MRS were also performed in older adults. RESULTS. Maximal and ATP-linked respiratory rate measured in platelets from older adults correlated significantly with muscle maximal respiration (r = 0.595; P = 0.003) and maximal ATP production (r = 0.643; P = 0.004; by 31 P-MRS) in the same individuals. Comparison of platelet bioenergetics in older and younger adults showed lower basal and ATP-linked respiration in older adults. Platelets from older adults also showed enhanced proton leak, which was due to increased protein levels of uncoupling protein 2, and correlated with gate speed (r = 0.58; P = 0.0019). While no significant difference in glycolysis was observed in older compared to younger adults, platelet glycolytic rate correlated with fatigability (r = 0.44; P = 0.016). CONCLUSION. These data advance the mechanistic understanding of age-related changes in mitochondrial function. Further, they suggest that measuring platelet bioenergetics provides a potential supplement or surrogate for muscle biopsy measurement and may be a valuable tool to study mitochondria in age-related decline of physical function.

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Section: L I N I C a L M E D I C I N Ementioning

confidence: 81%

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

See 1 more Smart Citation

Platelet bioenergetics correlate with muscle energetics and are altered in older adults

Braganza¹,

Corey²,

Santanasto³

et al. 2019

JCI Insight

Self Cite

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show abstract

“…Platelets from pulmonary hypertension patients show enhanced respiratory reserve capacity, which correlates with mean pulmonary artery pressure, pulmonary vascular resistance, and right ventricular stroke work index. Increased FA oxidation in these platelets is associated with augmented activity of carnitine palmitoyltransferase‐1, responsible for the formation of acylcarnitines, and ETC ‐complex II . Increased levels of acylcarnitine in CAD patients also indicates a metabolic shift in platelets, likely to be inflicted by metabolic disorder (hyperlipidaemia, diabetes) frequently leading to CAD.…”

Section: Lipids As An Energy Sourcementioning

confidence: 99%

“…47 Increased FA oxidation in these platelets is associated with augmented activity of carnitine palmitoyltransferase-1, responsible for the formation of acylcarnitines, and ETC -complex II. 52 Increased levels of acylcarnitine in CAD patients 5 also indicates a metabolic shift in platelets, likely to be inflicted by metabolic disorder (hyperlipidaemia, diabetes) frequently leading to CAD.…”

Section: Lipids a S An Energy Sourcementioning

confidence: 99%

Platelet lipidome: Dismantling the “Trojan horse” in the bloodstream

Chatterjee

2020

Journal of Thrombosis and Haemostasis

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The platelet‐lipid chapter in the story of atherothrombosis is an old one, recapitulated and revised in many contexts. For decades several stimulating facets have been added to it, both unraveling and increasing the perplexity of platelet‐lipid interplay and its pathophysiological consequences. The recent paradigm shift in our perspective has evolved with lipidomic analysis of the intraplatelet compartment and platelet releasate. These investigations have disclosed that platelets are in constant interaction with circulatory lipids, often reflected in their lipid repertoire. In addition, they offer a shielded intracellular space for oxidative lipid metabolism generating “toxic” metabolites that escape degradation by plasma lipases and antioxidant defense, circulate undetected by conventional plasma lipid profile, and deposited at atherosclerotic lesions or thrombus. Lipidomics divulges this silent invader in platelet vehicles, thereby providing potential biomarkers of pathologic manifestations and therapeutic targets to be exploited, which is surmised in this review.

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CPT1 regulates the proliferation of pulmonary artery smooth muscle cells through the AMPK-p53-p21 pathway in pulmonary arterial hypertension

et al. 2018

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Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity

Cited by 50 publications

References 54 publications

Platelet bioenergetics correlate with muscle energetics and are altered in older adults

Platelet bioenergetics correlate with muscle energetics and are altered in older adults

Platelet lipidome: Dismantling the “Trojan horse” in the bloodstream

CPT1 regulates the proliferation of pulmonary artery smooth muscle cells through the AMPK-p53-p21 pathway in pulmonary arterial hypertension

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