Circadian Immunity and Vascular Inflammation in Cardiovascular Disease Chronotherapy Windows: Time for a Re‐Assessment

ABSTRACT Circadian rhythms orchestrate cardiovascular physiology by regulating immune and inflammatory pathways. Disruption of these rhythms profoundly alters vascular homeostasis, thereby promoting the onset and progression of cardiovascular diseases (CVD). Evidence from experimental and clinical studies demonstrates that circadian misalignment aggravates myocardial infarction, stroke, and hypertension by enhancing oxidative stress, dysregulating immune cell function, and activating inflammasomes. At the cellular level, macrophages and neutrophils exhibit rhythmic metabolic and inflammatory activities driven by circadian transcriptional networks such as the CLOCK‐BMAL1 complex, PER/CRY repressors, and secondary loops involving REV‐ERBα and RORγ. Epigenetic regulators including p300, THRAP3, and SRC‐2 further refine this temporal control of vascular inflammation. Disruption of these oscillatory systems increases NADPH oxidase activity, elevates reactive oxygen species (ROS) production, and activates NF‐κB signaling, leading to endothelial dysfunction and vascular injury. Given these temporal dynamics, chronotherapy, defined as the strategic timing of medication administration to synchronize with endogenous biological rhythms, emerges as a crucial determinant for cardiovascular therapeutic efficacy. Chronotherapeutic strategies, including pharmacological targeting of circadian regulators such as REV‐ERBα agonists, hold promise for mitigating vascular inflammation and improving cardiovascular outcomes. This review summarizes current evidence linking circadian rhythm disruption to immunoinflammatory mechanisms in cardiovascular disease and highlights novel avenues for time‐based therapeutic interventions.