Inflammation and Immune Mechanisms in Atherosclerosis

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide, and atherosclerosis (AS) is a major underlying pathology. This review systematically examines the interplay between inflammation and immunity in AS. Disease initiation involves endothelial injury, formation of oxidized low-density lipoprotein (ox-LDL), and innate immune responses, including monocyte and macrophage infiltration and dendritic cell (DC) activation. Macrophages polarize to a proinflammatory M1 phenotype, phagocytose lipids to form foam cells, and release inflammatory mediators such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), thereby exacerbating plaque inflammation. DCs serve as a crucial link between innate and adaptive immunity by presenting antigens to CD4+ T cells. T helper 1 (Th1) cells facilitate inflammation through interferon-γ (IFN-γ), whereas regulatory T cells (Tregs) exert protective, anti-inflammatory effects. B cells have dual functions: B1 cells secrete immunoglobulin M (IgM) and provide protection, while B2 cells typically contribute to disease progression. In advanced lesions, immune cells cluster within the arterial wall to form arterial tertiary lymphoid organs (ATLOs), and the identification of neuro–immune–cardiovascular interfaces (NICIs) underscores the involvement of the nervous system. Chronic inflammation results in the thinning of the fibrous cap, thereby heightening the risk of plaque rupture and acute clinical events. Current therapies primarily target inflammatory pathways, including statins, colchicine, and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), whereas future strategies may focus on directly targeting immune cells.