CAMK1D and PI3 in low-density neutrophils are associated with the anti-hypertensive effects of valsartan.

Hypertension remains a significant global health issue. Low-density neutrophils (LDNs), a subset of neutrophils, contribute to vascular injury through immune activation. This study aimed to explore the effects of valsartan on LDNs in hypertension and to elucidate the molecular mechanisms underlying their role in therapeutic response. Newly diagnosed hypertensive patients received 80 mg/day valsartan for one month. Single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) collected before and after treatment. Mendelian randomization (MR) analysis was used to identify genes associated with valsartan response among the differentially expressed genes. Eleven cell subpopulations were identified, including four distinct LDN subtypes: CAMK1D, PI3, ISG15, and S100A12. Valsartan treatment reduced immune activation-related transcripts in LDNs, with decreased CAMK1D and increased PI3 expression. Lower MMP9 transcript levels in the PI3 subtype were linked to limited differentiation of LDNs into the CAMK1D subtype, with a preference for retention in the PI3 subtype, potentially contributing to valsartan's ehanced efficacy. Theses findings highlight CAMK1D and PI3 as LDN-related genes influencing valsartan response in hypertension, offering a foundation for future functional studies.