AXL in cardiovascular diseases: Pathophysiological insights and clinical perspectives

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, posing significant challenges to global health systems. Among the diverse molecular regulators implicated in CVD pathogenesis, AXL (AXL receptor tyrosine kinase)-a member of the receptor tyrosine kinase family that includes Tyrosine-protein kinase receptor TYRO3, AXL receptor tyrosine kinase, and MER proto-oncogene tyrosine-protein kinase (collectively referred to as the TAM family)-emerges as a pivotal player with multifaceted roles. This review comprehensively explores the biological functions of AXL in cardiovascular systems, emphasizing its dualistic nature in regulating processes such as apoptosis, inflammation, oxidative stress, and vascular remodeling. AXL exerts context-dependent effects across various cardiovascular cell types, including endothelial cells, vascular smooth muscle cells, macrophages, and cardiomyocytes, influencing key pathological mechanisms underlying atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, aneurysm rupture, and other cardiovascular conditions. Notably, AXL-mediated signaling through the GAS6/AXL axis reveals protective effects in certain settings while exacerbating damage in others. These findings underscore the complexity of AXL's role in cardiovascular health and disease. The review also highlights the therapeutic potential of targeting AXL in CVDs, discussing current challenges in designing cell-type-specific and context-sensitive interventions. By integrating emerging evidence, this review aims to advance understanding of AXL's role in cardiovascular pathology and inform the development of innovative, targeted therapeutic strategies.