Журнал кардиореспираторных исследований 2026. №3

Тема статьи

Modern molecular and pathogenetic mechanisms of endothelial dysfunction progression in patients with coronary artery disease (26-31)

Авторы

Nosirova D. A. , Tashkenbaeva E.N., Khayrilloeva M. Kh., Bipanshul

Учреждение

Samarkand State Medical University

Аннотация

Coronary atherosclerosis is a chronic progressive disease of the arterial wall, the pathogenesis of which is determined by a complex interplay of lipid metabolism disorders, endothelial dysfunction, chronic inflammation, immune responses, oxidative stress, cellular plasticity, and extracellular matrix remodeling. The modern concept of atherogenesis substantially expands the classical view of lipid accumulation within the vascular wall. It has been demonstrated that the progression of atherosclerotic plaques results from dynamic interactions among endothelial cells, monocytes/macrophages, lymphocytes, vascular smooth muscle cells, platelets, and cells of the innate immune system. The retention of atherogenic lipoproteins within the intima, their subsequent modification, endothelial activation, and recruitment of inflammatory cells play a key role in the initiation and progression of atherosclerosis. Oxidized low-density lipoproteins and cholesterol crystals are capable of activating the NLRP3 inflammasome, followed by the production of interleukin-1β and interleukin-18. Impaired efferocytosis, formation of the necrotic core, phenotypic switching of vascular smooth muscle cells, calcification, neovascularization, and the formation of neutrophil extracellular traps also play important roles in disease progression. Emerging evidence also highlights the significance of clonal hematopoiesis of indeterminate potential, epigenetic mechanisms, and non-coding RNAs in the development of the pro-inflammatory phenotype of vascular wall cells. The development of single-cell sequencing and spatial transcriptomics technologies has revealed substantial cellular and molecular heterogeneity within atherosclerotic plaques and has led to a shift from the simplified M1/M2 macrophage polarization model toward a concept encompassing multiple functionally distinct cellular states. Understanding these mechanisms opens new opportunities for personalized assessment of the risk of coronary atherosclerosis progression and for the development of targeted therapeutic strategies

Ключевые слова

coronary atherosclerosis, atherosclerotic plaque, endothelial dysfunction, LDL, inflammation, NLRP3 inflammasome, macrophages, vascular smooth muscle cells, epigenetics, non-coding RNAs, clonal hematopoiesis, calcification

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