Biomed J. 2026 Oct 9:101054. doi: 10.1016/j.bj.2026.101054. Online ahead of print.
ABSTRACT
BACKGROUND: Heme oxygenase-1 (HO-1) participates in vascular redox regulation, but its context-dependent relationships with ferroptosis-associated endothelial injury and vascular-cell functions remain incompletely defined.
MATERIAL AND METHODS: Human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), and human aortic smooth muscle cells (HASMCs) were examined using FAC/RSL3 treatment, hydrogen peroxide, iron chelator Dp44MT, HO-1 inducer cobalt protoporphyrin (CoPP), HO-1 inhibitor Zn(II) protoporphyrin IX (ZnPP), HO-1 knockdown, and HO-1 overexpression. Outcomes included viability, lipid peroxidation, Annexin V/PI staining, total assay-detectable cellular iron, mitochondrial Fe2+-associated fluorescence, ROS, protein abundance, proliferation, tube-network formation, and collagen-gel contraction.
RESULTS: FAC/RSL3 treatment produced cell injury accompanied by increased lipid peroxidation and sensitivity to liproxstatin-1. Dp44mT reduced FAC-associated total cellular iron and mitochondrial Fe2+ signals and attenuated several injury-associated readouts. Pharmacological and genetic modulation of HO-1 was associated with changes in FAC/RSL3/Dp44mT responses, ROS levels, proliferation, and tube network formation. In HASMCs, CoPP treatment was associated with reduced ROS levels and collagen-gel contraction, as well as altered protein abundance of GDF15 and WISP1.
CONCLUSIONS: The findings identify context-dependent associations between HO-1 modulation and vascular-cell responses in vitro. This study highlights HO-1 as a versatile regulator of vascular cell function, providing a critical molecular framework for developing novel therapeutic strategies to treat atherosclerosis and related cardiovascular diseases.
PMID:42854783 | DOI:10.1016/j.bj.2026.101054