Targeting the PHD2/HIF-1α/HO-1 pathway: A key role of trimetazidine in hypertensive nephropathy
Year: 2025
Type: article
Abstract: Objective This study seeks to unravel the effects of trimetazidine (TMZ) on hypertensive nephropathy (HN) in mice and its underlying mechanisms.Methods Sixty male 129 mice (8−10 weeks old) were randomly categorized into six groups (n = 10 per group): control, model, TMZ, TMZ + small interfering RNA targeting prolyl hydroxylase domain protein 2 (si-PHD2), TMZ + zinc protoporphyrin [ZnPP, a heme oxygenase-1 (HO-1) inhibitor], and TMZ + KC7F2 [a hypoxia-inducible factor-1 alpha (HIF-1α) inhibitor]. All groups except the control group received angiotensin II to induce HN models. TMZ was administered by gavage for 28 days, while the other TMZ-based groups received additional si-PHD2, ZnPP, or KC7F2. Blood pressure, renal function, proinflammatory cytokines, and kidney pathology were measured. Protein/mRNA levels of PHD2, HO-1, HIF-1α, and Collagen I were analyzed via reverse transcription quantitative polymerase chain reaction/Western blot.Results The model group showed increased blood pressure, renal injury, fibrosis, and elevated levels of PHD2, HIF-1α, HO-1, Collagen I, and inflammatory markers compared to the control group (P < 0.05). TMZ treatment alleviated renal damage and downregulated PHD2, while upregulating HIF-1α and HO-1. These effects were further enhanced by PHD2 knockdown (TMZ + si-PHD2), but reversed by the inhibition of HO-1 or HIF-1α (TMZ + ZnPP, TMZ + KC7F2).Conclusion TMZ improves HN in mice by modulating the PHD2/HIF-1α/HO-1 pathway.
Authors: Daqian Gu, Meixian Chen, Yuhui Yang, Chen Lu, Chao Li, Yi Lin
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415081825