Weili Qiao

Selenium deficiency is implicated in pulmonary arterial hypertension (PAH). This study investigated the effects of sodium selenite (SSE) on PAH and its underlying mechanisms. In a monocrotaline-induced PAH rat model, SSE treatment significantly improved right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and vascular remodeling. It reduced collagen deposition and partially restored the expression of Collagen 1 and SM22α. SSE upregulated glutathione peroxidase 3 (GPX3) expression and attenuated oxidative stress, as evidenced by enhanced SOD activity and decreased MDA levels. In vitro, SSE inhibited H₂O₂ and angiotensin II-induced proliferation, oxidative stress, and phenotypic switching in pulmonary artery smooth muscle cells (PASMCs), while upregulating GPX3 at both mRNA and protein levels. These findings demonstrate that SSE alleviates PAH by enhancing GPX3-mediated antioxidant defense and suppressing vascular remodeling, supporting its potential as a therapeutic strategy for PAH.

Pulmonary arterial hypertension (PAH) is characterized by cardiac remodelling. Glutaminolysis plays a crucial role in PAH‐induced remodelling. The metabotropic glutamate receptor 5 (mGluR5) may mediate this process. This study investigated whether or not the blockade of mGluR5 may attenuate PAH‐induced pathological cardiac remodelling. Pulmonary arterial hypertension was induced by intraperitoneally injecting male Sprague‐Dawley (SD) rats with 60 mg/kg of monocrotaline (MCT). 3‐((2‐Methyl‐4‐thiazolyl)ethynyl)pyridine (MTEP) (10 mg/kg intraperitoneally) was used as a therapeutic intervention to block mGluR5. Cardiac functions were assessed with right heart catheterization and electrocardiography. Alterations in protein expressions and inflammatory markers were investigated using western blot and enzyme‐linked immunosorbent assay (ELISA), respectively. Increased right ventricular systolic pressure (RSVP), elevated protein expressions of mGluR5, collagen types I and III and cartilage intermediate layer protein 1 (CILP1), enhanced phosphorylation of phosphatidylinositol 3‐kinase (PI3K), AKT and p38 mitogen‐activated protein kinase (P38MAPK), increased angiopoietin 2 (Ang 2) and vascular endothelial growth factor‐α (VEGF) protein expressions and elevated serum levels of interleukin 6 (IL‐6) and tumour necrotic factor α (TNF‐α) were observed in MCT‐induced PAH rats. MTEP improved hemodynamics and right ventricular hypertrophy. MTEP also attenuated MCT‐induced elevations in the protein expressions of mGluR5, collagen types I and III, CILP1, Ang 2 and VEGF and decreased PI3K, AKT and P38MAPK phosphorylations and inflammatory cytokine levels. Metabotropic glutamate receptor 5 blockade using MTEP ameliorates PAH‐induced pathological right cardiac remodelling via inhibiting the signalling cascade involving PI3K/AKT, P38MAPK, Ang 2 and VEGF.

Pulmonary arterial hypertension (PAH) is a decimating ailment described by chronic precapillary pulmonary hypertension, an elevated mean pulmonary arterial pressure with a normal pulmonary capillary wedge pressure, and a raised pulmonary vascular resistance resulting in increased right ventricular afterload culminating in heart failure and death. Current PAH treatments regulate the vasodilatory/vasoconstrictory balance of pulmonary vessels. However, these treatment options are unable to stop the progression of, or reverse, an already established disease. Recent studies have advanced a metabolic dysregulation, featuring increased glutamine metabolism, as a mechanism driving PAH progression. Metabolic dysregulation in PAH leads to increased glutaminolysis to produce substrate to meet the high-energy requirement by hyperproliferative and apoptosis-resistant pulmonary vascular cells. This article explores the role of glutamate metabolism in PAH and how it could be targeted as an anti-remodeling therapeutic strategy.