The Importance of Autoimmunity and Chronic Inflammation in the Development of Atherosclerosis: New Treatment Strategies
Alexander V. Blagov1*, Vladislav A. Kalmykov1, Olga N. Maltseva2, Alikhan Z. Asoyan1, Anastasia O. Maksaeva1,3, Alexander N. Orekhov1,4*
Journal of Angiotherapy 9(1) 1-8 https://doi.org/10.25163/angiotherapy.9110180
Submitted: 02 January 2025 Revised: 06 February 2025 Published: 10 February 2025
Abstract
Atherosclerosis, the leading cause of cardiovascular diseases, is a chronic inflammatory disorder driven by complex interactions between the innate and adaptive immune systems. Extensive research in both preclinical models and human studies has established the critical role of immune cells in sustaining vascular inflammation and promoting plaque development. Monocytes/macrophages, lymphocytes, neutrophils, mast cells, NK cells, and dendritic cells infiltrate atherosclerotic plaques, influencing disease progression through their activation and cytokine-mediated responses. Single-cell transcriptomic analyses have revealed distinct immune cell phenotypes, emphasizing their heterogeneity and functional dynamics in plaque formation, rupture, and resolution. Understanding the pathways involved in immune cell homing, activation, and regulation is essential for developing targeted therapies. Emerging anti-inflammatory interventions have shown promise in clinical trials, including IL-1β inhibitors (canakinumab), IL-6 antagonists (ziltivekimab), NLRP3 inflammasome inhibitors (colchicine, dapansutrile), and p38 MAPK inhibitors (losmapimod). These therapies aim to modulate inflammatory signaling and reduce cardiovascular risk. Additionally, nanoparticle-based imaging and drug delivery strategies are being explored to enhance precision medicine approaches in stabilizing plaques. However, balancing immune suppression with maintaining vascular homeostasis remains a challenge, necessitating further research to optimize therapeutic efficacy. This review provides an updated perspective on the immunological mechanisms underlying atherosclerosis and highlights novel anti-inflammatory strategies with potential clinical implications for cardiovascular disease management.
Keywords: Atherosclerosis, Immune Regulation, Inflammatory Pathways, Plaque Stabilization, Targeted Therapies
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