Circadian control of immune homeostasis in cardiovascular health and disease.

The circadian system is an important regulator of cardiovascular immune homeostasis. Emerging evidence suggests that daily timing of immune responses may influence cardiovascular disease progression by coordinating leukocyte trafficking, inflammatory thresholds, metabolic adaptation, and tissue repair across the 24-hour cycle. This review examines how core and auxiliary circadian regulators, including BMAL1, CLOCK, PER/CRY complexes, REV-ERBs, RORs, and systemic timing cues, shape immune-cell activation through transcriptional, epigenetic, metabolic, and neuroendocrine mechanisms. We further synthesize evidence on circadian coordination of leukocyte trafficking, particularly the CXCL12/CXCR4 axis, and discuss how disrupted timing may promote inappropriate leukocyte recruitment into the vascular wall. At the cellular level, circadian misalignment has been associated with altered macrophage polarization, inflammasome activation, and inflammatory injury, processes that may modulate atherosclerosis, myocardial ischemia-reperfusion injury, and post-infarction remodeling. Finally, we evaluate the translational potential and current limitations of chronopharmacology, emphasizing that time-of-day treatment strategies require careful consideration of clinical evidence, circadian phase assessment, chronotype, sex, age, comorbidities, and treatment feasibility. This evidence-weighted chrono-immunological perspective may help refine future research on cardiovascular inflammation and inform the development of more individualized prevention and therapeutic strategies.