CHEST Guidelines-Discordant-Regulation-of-microRNA-Between-Multiple

Discordant-Regulation-of-microRNA-Between-Multiple

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The study by Schlosser et al. investigates the regulation and expression of specific microRNAs (miRNAs) in different models and human cases of pulmonary arterial hypertension (PAH). Dysregulation of miRNAs is known to contribute to the pathobiology of PAH. The researchers measured miRNAs, including miR-17, -21, -130b, -145, -204, -424, and -503, in the plasma, lung, and right ventricle of common rodent models and in human subjects with PAH. They aimed to identify whether changes in miRNAs observed in rodent models could have correlates in human cases and potential utility as biomarkers or therapeutic targets.<br /><br />The study found that miRNA levels showed model-specific patterns of changes, with no consistent patterns across all animal models or between models and human PAH. In particular, the SU5416 plus chronic hypoxia (SuHx) model showed the greatest similarity to human PAH based on miRNA expression. Notably, miR-424 was found to be increased in both hypoxic mice and human PAH patients, suggesting miR-424 alterations may be a consistent feature in human PAH.<br /><br />Further analyses highlighted that the correlation between tissue and circulating levels of miRNAs varied by model. The study also conducted principle component analysis (PCA) to assess the similarity between each experimental model's molecular profile and human PAH. The SuHx model showed a closer resemblance to human PAH, which may indicated a better model for studying the disease mechanisms.<br /><br />Overall, the study concludes that miRNA-related mechanisms in PAH exhibit significant context-dependent variability. This complicates their use in diagnostics and treatment, emphasizing the need for a careful selection of appropriate models for PAH research that closely mimic the human condition. The research indicates the complexities of translational applications from animal models to human therapy.

Keywords

microRNAs

pulmonary arterial hypertension

PAH

miRNA dysregulation

biomarkers

therapeutic targets

SU5416 hypoxia model

miR-424

animal models

translational research