Current concepts of endothelial dysfunction: Severity, course, and clinical correlations

Endothelial dysfunction is a universal mechanism of injury, not specifically associated with any one nosology. It is characterized by insufficient production of vasodilators, prothrombotic and proinflammatory cell activation, and pathologically increased endothelial permeability. It is clinically heterogeneous, with regional variability in the expression of various pro- and anticoagulant factors. Essentially, all processes represent a continuum of genetic, epigenetic, transcriptomic, proteomic, metabolic, morphological, and functional changes. In 2023, a new concept for the pathogenesis of endothelial dysfunction as a systemic process was developed, enabling the prediction, prevention, and management of a number of diseases. Ten stages of endothelial damage and three degrees of severity are distinguished: mild, moderate, and severe. Mild endothelial dysfunction is characterized by reduced nitric oxide (NO) production and a noncritical decrease in ATP levels, coupled with increased energy consumption to adapt to increasing hypoxia. Clinically, this degree is most often associated with asthenic manifestations. Moderate/ severe ED is associated with progressive neurotransmitter imbalance, adhesion cell activation, microthrombosis, hypoxia, and neuroinflammation. The most pronounced clinical characteristics are secondary headache, cognitive, and anxiety-depressive disorders. Severe ED leads to endothelial cell death. Endothelial loss itself does not lead to thrombosis, but disruption of the parietal membrane integrity can affect blood rheology. Delayed neurological and systemic complications arise at this stage. Understanding the staging of damage is crucial for the development of individualized therapeutic interventions, from lifestyle modification to targeted therapy, with the search for a universal endothelial protector.

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