The paper “Spatial and temporal resolution of metabolic dysregulation in the Sugen hypoxia model of pulmonary hypertension (PAH)” explores the metabolic changes associated with the disease PAH, which is characterized by high blood pressure in the lungs and arteries leading to heart failure. Historically, other PAH studies have been conducted but they were limited to analyzing metabolites at a single point in time which doesn’t dive into the shift in their concentrations to represent this complex condition. Recognizing this gap, John Hopkin’s scientists utilized a mouse model that closely mimics the human PAH condition to examine how metabolic disturbances develop overtime across different tissues like heart, lungs and liver.
The study involved treating rodent models to develop symptoms similar to human PAH, allowing for investigating disease progression in a controlled environment. In addition, the researchers have also employed Aurora Biomed’s VERSA 1100 in the study to filter and prepare the tissue samples before they were analyzed by LC-MS. The precision in sample handling by the VERSA 1100 was vital for ensuring consistent metabolic profiling, which is essential when studying metabolic changes across different tissues. By using this approach, researchers were able to identify early biomarkers of PAH and understand the metabolic pathways involved. This further allows for targeted therapies and early interventions to treat the disease.
Male Wistar rats were treated with VEGFR2 inhibitor SU5416 and exposed to hypoxia to develop PAH characteristics (SuHx models). The diseased rats’ tissues were collected from heart, lungs and liver WHITE PAPERtissue after 7, 14 and 21 days post-induction providing a timeline to analyze how metabolic changes correlate with the development of the PAH disease. Control rats were also injected with the SU5416 vehicle but kept in normoxic (normal oxygen level) conditions to serve as a baseline for comparison with SuHx rats. Results showed that control rats did not exhibit the same metabolic and physical changes as the SuHx rats as they maintained normal metabolite levels and ventricular sizes throughout the experiment.
For tissue collection, the sample underwent preparation using Aurora’s VERSA 1100 via solid phase extraction in a 96-well plate format. More specifically the Impact Protein Precipitation Platesfrom Phenomenex. Aurora’s liquid handler deck layout allowed for the automation of this sample preparation protocol prior to LC-MS analysis. The data obtained was subjected to statistical analysis including PCA and PLSDA to showcase the differences in metabolic profiles
between the control and PAH-affected rats.
For full results and details please read the WHITE PAPER.