Myeloperoxidase Mechanisms in Cardiovascular Health

Myeloperoxidase (MPO) is a haem-containing enzyme produced predominantly by neutrophils and monocytes that catalyses the formation of potent oxidants from hydrogen peroxide and chloride or other halides. Within the vascular milieu, MPO-derived reactive species contribute to oxidative modification of lipids, proteins and extracellular matrix components. These modifications promote endothelial dysfunction, lipid accumulation in the intima and recruitment of inflammatory cells, thereby driving initiation and progression of atherosclerotic lesions. MPO-generated hypochlorous acid and nitrating intermediates impair high-density lipoprotein’s protective functions and destabilise fibrous caps by modifying collagen and matrix-metalloproteinases. Circulating MPO levels correlate with plaque burden and forecast adverse cardiac events, positioning MPO as both a mechanistic mediator and biomarker of cardiovascular risk. Interventions targeting MPO activity have shown promise in preclinical models for stabilising plaque, improving endothelial function and reducing thrombogenicity, signalling MPO inhibition as a compelling therapeutic avenue for cardiovascular disease management.

Research from Nature Portfolio

Recent studies have elucidated the three-dimensional structure of human MPO at near-atomic resolution, revealing conformational states that regulate access of hydrogen peroxide and halide substrates to the active site, and guiding the rational design of selective inhibitors. Building on structural insights, a novel small-molecule compound has been shown in a primate model to attenuate vascular inflammation, reduce oxidative modification of low-density lipoprotein and preserve endothelial nitric oxide bioavailability. In parallel, the development of a highly sensitive, activatable fluorescent probe permits non-invasive imaging of MPO activity in early atherogenesis, enabling real-time assessment of oxidative burden within arterial walls and offering a tool for monitoring therapeutic response.

Myeloperoxidase Mechanisms in Cardiovascular Health publication trend

The graph below shows the total number of articles in myeloperoxidase mechanisms in cardiovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

Myeloperoxidase (MPO): A heme-containing peroxidase enzyme released by neutrophils that generates reactive oxidants from hydrogen peroxide and halide ions.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen, including hydrogen peroxide and superoxide, which can damage cellular structures.

Hypochlorous acid (HOCl): A powerful oxidant produced by MPO from hydrogen peroxide and chloride, capable of chlorinating and oxidising biomolecules.

Atherosclerosis: A chronic inflammatory disease characterised by lipid accumulation, immune cell infiltration and fibrous plaque formation in arterial walls.

Endothelial dysfunction: Impaired ability of the vascular endothelium to regulate vasodilation, thrombosis and inflammatory responses, often an early step in atherogenesis.

References

1. Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives. Medical Sciences (2018).