Light reprograms cardiac circadian gene networks

The heart is a key regulator of blood flow and systemic homeostasis, and its function is tightly regulated by circadian rhythms, synchronizing parameters like heart rate and blood pressure with time of day. At its core is the heart’s circadian clock, a 24-hour transcriptional-translational feedback loop driven by the BMAL1:CLOCK complex, which binds to E-box elements to activate circadian genes. PER and CRY proteins inhibit BMAL1:CLOCK, forming a negative feedback loop. This mechanism regulates rhythmic gene expression, producing proteins important for heart function. Disrupting these rhythms, like nighttime light exposure, leads to cardiovascular disease. Previous work in our lab found light to directly influence cardiac gene expression, but the specific genes remain unknown. We hypothesize that light influences the expression of a subset of cardiac genes that are normally regulated by the circadian clock’s endogenous cycling. Two groups of 24 C57BL/6 mice were entrained to a 12-hour light/12-hour dark (LD) cycle. One group remained in LD, while the other was transferred to constant darkness (DD). For the LD group, time was recorded using Zeitgeber time (ZT), which references light induction, whereas DD samples were collected using Circadian time (CT), reflecting endogenous rhythms. Mice were sacrificed by CO 2 followed by cervical dislocation every 4 hours starting at ZT23 for 24 hours, yielding six time points, with four hearts collected at each point. Left ventricles were isolated and stored at -80°C. Total RNA was extracted using TRIzol reagent and run on Affymetrix Mouse Gene 2.0ST microarrays. Data were analyzed in Agilent GeneSpring, focusing on the dark-light (D:L) transition (ZT23-ZT03) and filtering for genes with >1.5 fold change (FC) in LD but not DD. Of 33,793 genes analyzed, 52 candidates met these criteria, suggesting potential light responsiveness. Three genes were selected for validation: Cryptochrome 1 (Cry1), Rev-Erbβ (Nr1d2), and Nuclear receptor 4A1 (Nr4a1), each with known roles in cardiac circadian regulation. Cry1, a repressor of CLOCK:BMAL1, showed a stronger decrease in LD (ZT23, 70±1 RFU vs. ZT03, 47±4 RFU; 1.50 FC) compared to DD (CT23, 67±4 RFU vs. CT03, 54±2 RFU; 1.24 FC). Nr1d2, a transcriptional repressor of Bmal1 with roles in lipid metabolism and inflammation, showed a stronger increase in expression in LD (ZT23, 49±5 vs. ZT03, 108±30; 2.20 FC), versus DD (CT23, 49±9 vs. CT03, 53±7; 1.09 FC). Nr4a1, which supports metabolic and mitochondrial function, showed a stronger increase in LD (ZT23, 107±4 vs. ZT03, 183±14; 1.71 FC), versus DD (CT23, 136±20 vs. CT03, 122±8; 1.11 FC). These findings support our hypothesis that light exposure alters the expression of cardiac genes normally regulated by endogenous circadian cycling. Ongoing phase-shift experiments will further confirm whether these genes are directly induced via photosensitive pathways. Funding: Canadian Institute of Heart Research (CIHR) and Heart and Stroke Foundation This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.