2026/03/01 by Esraa M. Zeidan, Sai Aparna Nagarajan, A Sydykov +10 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer, Hypoxia, and Metabolism #Nitric Oxide and Endothelin Effects #Pulmonary Hypertension Research and Treatments
paper · doi:10.14814/phy2.70804
openalex publication_date 2026/03/01 · openalex created_date 2026/03/12 · openalex updated_date 2026/07/23
Abstract Mitochondrial reactive oxygen species (mtROS) have been implicated in the development of chronic hypoxia‐induced pulmonary hypertension (PH), potentially through hypoxia‐inducible factor‐1α (HIF‐1α) stabilization. However, the role of mtROS in HIF‐1α stabilization, PH development, and the therapeutic potential of antioxidant treatment remains controversial. Mice were exposed to hypoxia (10% O 2 ) for 4 weeks to induce PH and treated with mitochondria‐targeted antioxidant mitoTEMPO or its carrier control, triphenylphosphonium (TPP + ). Cell proliferation was evaluated in mouse pulmonary arterial smooth muscle cells (PASMCs) by BrdU incorporation. HIF‐1α stabilization and downstream target expression were investigated in mouse lung carcinoma epithelial (CMT167) cells and isolated mouse and human PASMCs under different hypoxic conditions. In vivo mitoTEMPO treatment did not affect chronic hypoxia‐induced PH compared to TPP + . In vitro, mitoTEMPO treatment did not inhibit hypoxia‐induced mouse PASMCs proliferation but enhanced proliferation under normoxic conditions. In vitro exposure of CMT167 cells and mouse or human PASMCs to mitoTEMPO or TPP + did not alter HIF‐1α protein levels or expression of its downstream targets lactate dehydrogenase A ( Ldha ) and pyruvate dehydrogenase kinase 1 ( Pdk1 ) under normoxic (21% O 2 ) or hypoxic (1% or 10% O 2 ) conditions after 24 h. These findings do not support a therapeutic benefit of mitoTEMPO in hypoxia‐induced PH.