Intense light mitigates hypoxia-induced right ventricular remodeling and dysfunction through reducing inflammation associated with PF4+ resident macrophages

Hypoxia-induced right ventricular (RV) remodeling and dysfunction present a significant health risk to populations experiencing prolonged hypoxic conditions. Intense light, a noninvasive and easily implemented intervention, has previously been reported to exert cardioprotective effects by improving myocardial ischemia. However, whether intense light provides protective benefits against RV remodeling and the underlying mechanisms remain largely unexplored. In this study, we established mouse models exhibiting RV remodeling and dysfunction through long-term hypoxia to investigate the protective effects of intense light. Echocardiography, hemodynamic parameters measurements, and Fulton index assessments were employed to evaluate RV dysfunction and remodeling. Additionally, single-nuclei RNA sequencing, immunohistochemistry, immunofluorescence, and western blotting analyses were conducted to identify targeted genes in macrophage-associated inflammation within the heart. The results indicate that intense light significantly alleviates hypoxia-induced RV remodeling and dysfunction in mice. Intense light may mediate macrophage-associated inflammation through differentially expressed genes, including PF4, as well as the quantity of macrophages in the right ventricles (RVes). Resident macrophages (Res_Macro) demonstrate cardioprotective effects when intense light is applied, which mitigates RV remodeling. Our findings also suggest that PF4 expression and the presence of PF4⁺ resident macrophages (Res_PF4⁺_Macro) are linked to the attenuation of RV remodeling by intense light. Macrophage PF4 expression and the quantity of PF4⁺ macrophages in the RVes are closely associated with the levels of RV remodeling and dysfunction. This study unveils a novel noninvasive approach for the prevention of RV remodeling and dysfunction induced by hypoxia, and indicates that Res_PF4⁺_Macro and PF4 expression could be potential intervening targets.