Therapeutic potential of magnesium diboride nanosheets in PAH-associated right heart failure: Integrated multi-omics analysis reveals ferroptosis suppression via LC3/ATG5/NCOA4/FTH1 pathway.

Pulmonary arterial hypertension (PAH) is a progressive obstructive pulmonary vasculopathy characterized by pathological vascular remodeling driven by excessive cellular proliferation, apoptosis resistance, chronic inflammation, fibrotic deposition, and dysregulated vasoconstriction. As the disease advances, these vascular abnormalities culminate in right heart failure (RHF). The right ventricular (RV) initially undergoes compensatory hypertrophy but ultimately decompensates, manifesting as chamber dilation, impaired contractility, and progressive fibrosis. Despite the critical determinant role of RV functional reserve in patient survival and prognosis, but no clinically validated interventions directly address RV adaptation. Molecular hydrogen (H2), a biologically safe therapeutic agent with exceptional antioxidative, anti-inflammatory, anti-apoptotic properties and autophagic flux-modulating activities, has demonstrated organoprotective efficacy in cardiovascular and cerebrovascular disorders. Nevertheless, its therapeutic potential in mitigating PAH-induced RHF remains unexplored. Clinical translation is hindered by hydrogen's high explosivity and low bioavailability, necessitating the development of safer and more efficient delivery strategies. This study developed novel hydrogen-releasing magnesium diboride nanosheets (MBNs), and employs an integrated transcriptomic-proteomic approach to investigate the cardioprotective effects of MBNs against PAH-induced RHF and elucidate its underlying molecular targets and mechanisms of action.