From the Guidelines
Myeloperoxidase (MPO) is a crucial enzyme that catalyzes chlorinating reactions, linking oxidative stress to inflammation and endothelial damage, as evident in the context of chronic kidney disease (CKD) 1. The function of MPO enzyme is multifaceted, playing a significant role in the immune system's defense against pathogens. Key aspects of MPO's function include:
- Catalyzing the production of hypochlorous acid from hydrogen peroxide and chloride ions during the respiratory burst, creating a powerful antimicrobial system
- Being stored in the azurophilic granules of neutrophils and released when these cells are activated during infection or inflammation
- Serving as a biomarker for inflammatory conditions, with elevated levels often indicating active inflammation or infection MPO's clinical significance extends to its potential role in atherosclerosis and heart disease risk, as it may contribute to oxidative damage in blood vessel walls. However, the most recent and highest quality evidence highlights its importance in the context of oxidative stress and inflammation, particularly in CKD patients 1. In real-life clinical medicine, understanding the function of MPO enzyme is essential for managing conditions associated with oxidative stress and inflammation, and MPO should be considered a key player in the pathogenesis of cardiovascular disease in dialysis patients.
From the Research
Function of Myeloperoxidase (MPO) Enzyme
- Myeloperoxidase (MPO) is an enzyme that plays an essential role in the antimicrobial and antiviral system of humans 2
- MPO is physiologically expressed in circulating neutrophils, monocytes, and some tissue macrophages, including microglia 2
- The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions by H2O2, thereby producing respective hypohalous acids (HOX) 2
Role of MPO in Disease
- MPO is a key factor in a great number of conditions, including cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases, and immune-mediated diseases 2
- Excessive levels of MPO have been linked to various disorders, including cancer, cardiovascular, and neurological disorders 3
- MPO-derived oxidants can promote tissue damage during inflammation, making it a potential therapeutic target for the treatment of various diseases 2, 3, 4, 5
Mechanism of Action
- MPO catalyzes the production of the potent oxidant hypochlorous acid (HOCl) and the catalytic consumption of NO via the enzyme's NO oxidase activity 4
- MPO can also influence endothelial function via non-catalytic, cytokine-like activities 4
- The enzyme's actions can lead to the generation of dysfunctional lipoproteins, reduced NO availability, endothelial dysfunction, impaired vasoreactivity, and atherosclerotic plaque instability 5
Non-Canonical Functions of MPO
- Emerging evidence indicates that MPO can directly or indirectly impact immune cells and tissue responses in homeostatic and disease states 6
- MPO can affect neutrophil longevity, activation, and trafficking in inflammation, as well as interact with other immune cells and barrier-forming endothelial and epithelial cells 6
- MPO is involved in cancer progression and can shape disease outcomes through its interactions with various cellular compartments 6