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

ABSTRACT: Nocturnal hypertension is a strong predictor of cardio cerebrovascular disease (CVD), yet its underlying mechanisms remain largely unknown. In this study, we identified CD36 as a key regulator of blood pressure (BP) rhythms and as a gatekeeper of nocturnal hypertension. Its deficiency disrupts circadian BP rhythms.We continuously monitored 48-hour BP using telemetry in CD36 global knockout (KO) mice and renal proximal tubule-specific CD36 KO mice. We also collected serum samples and ambulatory blood pressure monitoring (ABPM) data from patients with nocturnal hypertension to assess the relationship between CD36 expression and nocturnal hypertension. A comprehensive screening of various factors affecting BP and circadian rhythms was conducted to explore the molecular mechanisms involved, utilizing RNA sequencing, calorimetry, enzyme-linked immunosorbent assay (ELISA), co-immunoprecipitation, immunofluorescence assays, and echocardiography. 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE335135 | GEO | 2026/06/15

REPOSITORIES: GEO