Inflammatory Mechanisms in Action: Unraveling Their Central Role in Atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the accumulation of lipid plaques that reduce blood flow. Its pathogenesis begins with endothelial dysfunction, triggered by hemodynamic stress, oxidized LDL (oxLDL) and risk factors (hypertension, smoking), which increases vascular permeability and facilitates lipid infiltration in the intima. Subsequently, innate immunity is activated: monocytes attach to the endothelium by adhesion molecules (VCAM-1/ICAM-1), migrate to the subendothelial space and differentiate into macrophages. These, when phagocytosing oxLDL through receptors (CD36, LOX-1), are transformed into foam cells, releasing pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and activating the NLRP3 inflammasome in response to cholesterol crystals or oxidative stress. This complex amplifies inflammation by processing IL-1β, perpetuating cell recruitment and plaque progression. The adaptive immune response involves T lymphocytes (Th1, Th17) and B cells, which exacerbate inflammation, while mediators such as chemokines (MCP-1) facilitate leukocyte migration. Plaque instability arises from collagen degradation (via metalloproteinases), necrotic core expansion, and defective angiogenesis, increasing the risk of rupture and acute events (infarction, stroke). Currently, therapies seek to modulate these mechanisms through anti-inflammatory drugs (anti-IL-1β, colchicine), NLRP3 inflammasome inhibitors and microRNA regulation (miR-33) or epigenetics. This approach is crucial, given that cardiovascular complications associated with atherosclerosis are the leading cause of global death, with 1.9 million deaths annually in Latin America.