Determining the Effect of Obesity on Pulmonary Arterial Hypertension (PAH) in a Mouse Model
Session Number
MEDH 40
Advisor(s)
Dr. Sanda Predescu, Rush University Medical Center
Discipline
Medical and Health Sciences
Start Date
17-4-2025 11:40 AM
End Date
17-4-2025 11:55 AM
Abstract
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.
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.