Apolipoproteins in circulation: At the interface of thrombosis and stroke initiation

Ischemic stroke, a leading cause of death and disability worldwide, arises predominantly from atherosclerosis and thromboembolic occlusion of cerebral arteries. While advancements in acute interventions such as thrombolysis and thrombectomy have improved outcomes, the identification of upstream molecular drivers remains essential for better prevention and risk stratification. Among these, circulating apolipoproteins, the structural and regulatory proteins of lipoprotein particles, are increasingly recognized as pivotal mediators at the intersection of lipid metabolism, inflammation, endothelial dysfunction and thrombosis. This review summarizes recent evidence on the diverse roles of apolipoproteins in systemic vascular biology and their contributions to stroke initiation. We examine how specific apolipoproteins influence atherogenesis, plaque instability, coagulation factor dynamics, immune-endothelial interactions and platelet adhesion. Emerging data suggest that functional imbalances among apolipoproteins, independent of conventional lipid levels, may serve as superior predictors of stroke risk and reveal novel mechanistic links between dyslipidemia, immune cell activation and thrombo-inflammation. By bridging insights from lipidology, vascular biology and thrombosis research, we position apolipoproteins as promising biomarkers and therapeutic targets to reduce the burden of ischemic stroke and improve cerebrovascular health.