CD36 gates nocturnal hypertension by regulating inactive period blood pressure variation via renal AMPK/HDAC5/PER1 axis

Our telemetry data revealed significantly elevated BP during the daytime (inactive period) in both CD36 global KO and renal proximal tubule specific KO mice compared to their control counterparts. Furthermore, levels of platelet CD36 negatively correlated with the severity of nocturnal hypertension in humans. Mechanistically, CD36 modulates BP rhythms through the AMPK/HDAC5/PER1 pathway: its deficiency activates phosphorylated AMPK, leading to the dissociation of the HDAC5-PER1 complex, enhancing PER1 nuclear accumulation, and desynchronizing the oscillations of intrarenal reninangiotensin-aldosterone system (RAAS) genes and clock-controlled genes (CCGs), ultimately disrupting BP rhythm.

Our findings highlight CD36 as a critical integrator that links renal clocks to BP homeostasis, establishing it as a potential predictor and therapeutic target for nocturnal hypertension.