Determining the Effect of Obesity on Pulmonary Arterial Hypertension (PAH) in a Mouse Model

Pulmonary arterial hypertension (PAH) is a sex-biased disease characterized by pulmonary vascular remodeling, increased resistance to blood flow through vasculature, and right heart failure. This project aimed to determine the relationship between PAH and obesity, a comorbidity of PAH, on the lung phenotype of a murine model. This model displays both stages of PAH: pulmonary arterial thickening, and obliteration of small to medium pulmonary vessels, recapitulating the human disease. To generate the mouse model of PAH and obesity, genotypically selected intersectin-1 knockdown (KOITSN+/-) mice were subjected to a high-fat diet for 12 weeks, with weights being measured once every week. Additionally, lipoplexes/EHITSN- DNA (100μg EHITSN-DNA per injection), 8 nmoles liposomes/1 μg myc-EHITSN DNA were delivered to murine lungs through retro-orbital injections every 48 hours for 21 days. The lungs were excised, set in 4% paraformaldehyde, embedded in paraffin, and sectioned 5 μm thick. I have analyzed 3 obese and 3 non-obese male mice with PAH, looking for lung tissue differences. Micrographs were taken using 20x and 40x objectives to visualize PAH-affected lesions and vessels. The data found shows that obesity worsens the outcome of PAH by increasing the thickness of muscularized vessels and the frequency of pulmonary lesions.