Integrated metabolomics and mechanism to reveal the protective effect of kaempferol on pulmonary arterial hypertension

Currently, there have been breakthroughs in the study of the underlying mechanisms of pulmonary arterial hypertension, but treatment is still challenging. The aim of this study was explore the effect of kaempferol in PAH and discover the mechanism of this process. First, we assessed the effect of kaempferol in animal models of PAH. The echocardiography and pressure-volume admittance catheter data showed that kaempferol could improve right ventricular function and alleviate the progression of PAH. Moreover, morphometric analysis of the lung vasculature indicated that pulmonary vascular remodeling could be reduced by kaempferol. The expression of autophagy-related proteins and autophagic processes were evaluated by western blotting and mRFP-GFP-LC3 fluorescence microscopy, the results indicated that autophagy played an important role in the process by which kaempferol prevents PAH. Moreover, we performed untargeted and targeted plasma metabolomics analysis on rat models of PAH and used multivariate analysis to reveal multiple pathways and targets. Consequently, we identified 247 plasma biomarkers that were tightly linked to the preventive effects of kaempferol, which were mainly related to amino acid metabolism and arachidonic acid metabolism. In conclusion, kaempferol could effectively alleviate the development of PAH by regulating abnormal autophagy and metabolic disorders, providing a novel perspective on the treatment of PAH.