Date of Award
Spring 5-2-2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
First Advisor
Alexandra Racanelli
Second Advisor
Diego Loayza
Academic Program Adviser
Diego Loayza
Abstract
Chronic obstructive pulmonary disease (COPD) affects approximately 200 million people worldwide and is the fourth leading cause of death. Current treatments are directed at blocking lung inflammation to stop lung destruction but cannot stop the progression of COPD. However, emerging data points towards endothelial cells (ECs) in the lung microvasculature damage. We used an in vitro model of emphysema by instilling elastase into the lungs of mice where EC leucine-rich alpha-2-glycoprotein-1 (LRG1) was deleted in adult mice. We found that vascular dysfunction in the murine elastase model showed persistently elevated expression of LRG1 in pulmonary capillary endothelial cells (PCECs). LRG1 is a secreted glycoprotein that binds to the TGF-𝜷 accessory receptor and disrupts normal cellular interactions in the ECs necessary for formation and maintenance of blood vessels, thereby causing a hypoxic and immunosuppressive environment and forming aberrant blood vessels. We hypothesize that elevated levels of LRG1 in PCECs drives EC dysfunction, leading to disruption of alveolar capillary matrix and preventing proper repair. I have studied this by constructing an inducible deletion of LRG1 specifically in lung ECs in mice, and my data suggests that loss of LRG1 is protective against an emphysema model induced by elastase administration in the lung.
Recommended Citation
Kuang, Amy, "The role of LRG1 in pulmonary capillary endothelial cells in vascular dysfunction in COPD" (2025). CUNY Academic Works.
https://academicworks.cuny.edu/hc_sas_etds/1350
