Challenges and Prospects for Clinical Application of Specialized Pro-resolving Lipid Mediators and Their Synthetic...

Atherosclerosis, a major cause of cardiovascular diseases, has a complex pathogenesis involving lipid metabolism disorders and chronic inflammation in the vascular wall. Specialized Pro-resolving Mediators (SPMs) are endogenous lipid molecules that are synthesized from polyunsaturated fatty acids and can switch inflammation from the active phase to resolution. As a result, SPMs are of great clinical interest, as they have the potential to improve the course of atherosclerosis by reducing inflammation and promoting the stabilization of atherosclerotic plaques. However, the direct clinical application of SPMs is limited by a number of objective problems, including their chemical instability, the complexity of targeted delivery to atherosclerotic lesions, and a lack of clinical data on the long-term safety of chronic exposure to immune-modulating pathways. This review critically analyzes the key barriers to the translation of SPMs into clinical practice. The main focus is on strategies to overcome these limitations, in particular, the development of stable synthetic analogues of SPMs and innovative delivery systems. Issues of the therapeutic window, the selection of optimal points of application for therapy, and the prospects for integrating SPMs into existing treatment standards are discussed. Thus, despite the lack of clinical data on the use of SPMs for the treatment of atherosclerosis, the development of stable synthetic analogues and targeted delivery systems is a promising direction for the creation of a fundamentally new class of cardiovascular drugs.