Hypoxic pulmonary hypertension (HPH), a form of pulmonary hypertension (PH) caused by hypoxia, could cause serious complications and has a high mortality rate, and no clinically effective treatments are currently available. In this study, we established an HPH preclinical model in rats by simulating clinicopathological indicators of the disease. Our results showed that high mobility group box-1 protein (HMGB1) aggravated the clinical symptoms of HPH. We aimed at establishing protocols and ideas for the clinical treatment of HPH by identifying downstream HMGB1 binding receptors. Our investigation showed that continuous hypoxia could cause significant lung injury in rats. ELISA and western blotting experiments revealed that HPH induces inflammation in the lung tissue and increases the expression of a hypoxia-inducible factor. Testing of lung tissue proteins and in human pulmonary artery endothelial cells revealed that the HMGB1-mediated increase in the receptor for advanced glycation end products (RAGE) expression promoted inflammation. In summary, we successfully established an HPH rat model providing a new model for preclinical HPH research and elucidated the role of HMGB1 in HPH. Furthermore, we describe that HMGB1 induced inflammation in the HPH model via RAGE, causing severe lung dysfunction. This study could potentially provide novel ideas and methods for the clinical treatment of HPH.
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| http://dx.doi.org/10.1155/2022/6823743 | DOI Listing |
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