Abstract
Atherosclerosis represents a chronic inflammatory disease of the arterial wall and remains a principal cause of cardiovascular morbidity and mortality. Macrophages critically govern lesion initiation, progression, and destabilization, and accumulating evidence indicates that protein kinases are key regulators of their phenotype and function. This systematic review synthesizes data from 162 publications encompassing 76 kinases to delineate the contribution of macrophage-associated kinase signaling to atherogenesis. The identified kinases span major families, including AGC, CaMK, CMGC, Ste20, and tyrosine kinases, each exerting distinct regulatory effects on macrophage survival, polarization, lipid handling, efferocytosis, and inflammatory activation. Several kinases, such as CaMK2γ, CaMK4, DCLK1, Trib1, and STK25, exhibit pro-atherogenic activity by promoting foam cell formation, expanding the necrotic core, and propagating inflammatory pathways. Conversely, kinases, including STK11 and the context-dependent mediator Akt1, exhibit protective or dual functions that contribute to metabolic homeostasis and reparative macrophage states. Despite substantial mechanistic insights and the established therapeutic utility of kinase inhibitors in oncology, clinical translation in the context of atherosclerosis remains limited. This review consolidates current knowledge, identifies critical gaps, and outlines prospective avenues to target macrophage-specific kinase pathways as novel therapeutic strategies for atherosclerosis.