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Investigating Cardiac Metabolism in the Isolated Perfused Mouse Heart with Hyperpolarized [1-13C]Pyruvate and 13C/31P NMR Spectroscopy
Published on: April 21, 2023
[The intracellular metabolism of neutrophils under different forms of ischemic heart disease]
Insights
Ischemic heart disease patients show increased neutrophil reactive oxygen species production and decreased catalase activity. This metabolic shift, linked to hypoxia and immune complexes, contributes to neutrophil dysfunction and damage.
Area of Science:
- Biochemistry
- Immunology
- Cardiology
Context:
- Investigates intracellular metabolism of neutrophils in patients with ischemic heart disease (IHD).
- Compares metabolic profiles of neutrophils in IHD patients versus controls.
- Examines metabolic changes across different severities of IHD, from unstable angina to myocardial infarction.
Purpose:
- To elucidate the alterations in neutrophil intracellular metabolism during ischemic heart disease.
- To correlate changes in neutrophil function with disease severity and specific biomarkers.
- To understand the role of oxidative stress and immune complexes in IHD-related neutrophil dysfunction.
Summary:
- Patients with IHD exhibit heightened neutrophil production of reactive oxygen species (ROS) alongside reduced intracellular catalase activity and elevated lactate levels in phagocytes.
- Neutrophil metabolic activation, driven by increased circulating immune complexes in severe IHD (myocardial infarction), is not counterbalanced by enhanced antioxidant enzyme activity.
- Maximal activation of neutrophil NAD(F)N-oxidase and a twofold increase in intracellular lactate were observed in Q-wave myocardial infarction patients, suggesting hypoxia-induced intracellular acidosis and phagocyte destruction.
Impact:
- Findings suggest that increased lactate production in neutrophils during myocardial ischemia contributes to intracellular acidosis, oxidative stress, and phagocyte destruction.
- Highlights the imbalance between pro-oxidant activity and antioxidant defense in neutrophils during IHD.
- Provides insights into the cellular mechanisms underlying neutrophil dysfunction in ischemic heart disease, potentially informing therapeutic strategies.
Abstract:
The article deals with the results of study of the intracellular metabolism of neutrophils in 96 patients including 56 (58.3%) patients with ischemic heart disease. It is established that in patients with ischemic heart disease as compared with patients without ischemic heart disease occurs the increase of neutrophils producing of active forms of oxygen against the background of decrease of intracellular activity of catalase and increase of concentration of lactate in phagocytes. Under severing of ischemic heart disease from unstable stenocardia to cardiac infarction the activation of oxygen-depending metabolism of neutrophils conditioned by increase of concentration of immune complexes circulating in blood was not compensated by increasing of intracellular activity of enzymes of system of antioxidant defense. The maximum activation of NAD(F)N-oxidase of neutrophils (production of superoxide anion-radical) was detected in patients with cardiac infarction with Q-wave. This condition was accompanied by maximal increase of concentration of lactate in phagocytes up to twice higher exceed the level of indicators in patients without ischemic heart disease. It can be assumed that in conditions of acute hypoxia occurring under myocardium ischemia in patients with ischemic heart disease, the lactate production increases in neutrophils hence the triggering of development of intracellular acidosis, impact of oxygen-depending factors and phagocytes destruction.
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