Adrenergic receptors on immune cells in cardiovascular disease: signaling plasticity, biased agonism, and therapeutic opportunities.

Sustained sympathetic nervous system activation is a hallmark of hypertension, atherosclerosis, ischemic injury, stroke, and heart failure. While adrenergic receptor (AR) biology is often discussed in cardiomyocytes, vascular smooth muscle, and endothelium, immune cells also express α1-, α2-, and β-ARs, enabling leukocytes to directly sense catecholamine tone and translate it into inflammatory or pro-resolving programs. In this review, we integrate subtype-specific signaling logic (α1AR-Gq/PLC/Ca2+; α2AR-Gi with reduced cAMP; βAR-Gs with cAMP-PKA/EPAC) with key regulatory features that determine outcomes in vivo, including receptor phosphorylation, trafficking and desensitization, compartmentalized signaling, and noncanonical pathways mediated by Gβγ and β-arrestins. We highlight how these mechanisms create context dependence across immune lineages and disease stages, shaping chemotaxis and adhesion, cytokine production, effector functions (for example ROS generation, antigen presentation, and cytotoxicity), and resolution programs such as IL-10-linked responses and efferocytosis. Across CVD contexts, immune cell AR signaling can amplify injury or constrain inflammation, thereby influencing endothelial dysfunction, vascular remodeling, fibrosis, microvascular impairment, and long-term organ function. Finally, we outline translational priorities, including improved mapping of AR expression and signaling states in human immune compartments, immune-phenotyped evaluation of AR-targeted therapies, and precision approaches using subtype-selective or biased ligands to modulate inflammation while preserving essential host defense and repair.