Inflammation-Driven Plaque Erosion in Atherosclerosis: A Focus on Complement System Pathways

Complement system activation is implicated in various stages of atherogenesis, from fatty streak formation to plaque destabilization and thrombus formation, with its dreadful clinical sequelae such as myocardial infarction, stroke and premature death. In this review, we consider these issues and explore recent studies on complement activation in atherosclerotic plaque initiation and progression.

Complement pathways impact plaque stability and healing through the modulation of inflammatory processes. Recent studies indicate that complement components, notably C3 and C5b-9, accelerate atherosclerosis progression through their interactions with endothelial cells, smooth muscle cells, and immune cells. Nonetheless, the beneficial versus deleterious effects of complement activation at different stages of atherogenesis remains a matter of ongoing debates. Research also investigates therapies targeting the complement cascade to mitigate plaque erosion and rupture. This review explores the ongoing debates surrounding complement activation in atherogenesis. We bring forward controversial findings and therapeutic strategies aimed at modulating complement cascade activation with the ultimate goal to reduce the burden of atherosclerotic cardiovascular disease.\.