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

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Hypoxia-induced right ventricular 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 right ventricular remodeling and the underlying mechanisms remain largely unexplored. In this study, we established mouse models exhibiting right ventricular 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 right ventricular 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 right ventricular 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. Resident macrophages (Res_Macro) demonstrate cardioprotective effects when intense light is applied, which mitigates right ventricular remodeling. Our findings also suggest that PF4 expression and the presence of PF4 + resident macrophages (Res_PF4 + _Macro) are linked to the attenuation of right ventricular remodeling by intense light. Macrophage PF4 expression and the quantity of PF4 + macrophages in the right ventricles are closely associated with the levels of right ventricular remodeling and dysfunction. This study unveils a novel noninvasive approach for the prevention of right ventricular remodeling and dysfunction induced by hypoxia, and indicates that Res_PF4 + _Macro and PF4 expression could be potential intervening targets.

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