Sex-Dependent Differences in Lung Vascular Regeneration

Introduction/Background: Impaired lung regeneration and repair are implicated in the pathogenesis of chronic lung diseases. Stimulating the regenerative ability of the lungs would be a promising strategy for chronic lung diseases. There are sex-related differences in lung diseases. Development of the sex-dependent treatment may lead to more efficient strategy for lung diseases, and we need to understand the mechanism. Angiogenesis-formation of new capillary blood vessels-plays key roles in organ regeneration. There are sex-dependent differences in transcriptomics of endothelial cells (ECs) and angiogenic activity. We have reported that endothelial signaling is necessary for regenerative lung growth after unilateral pneumonectomy (PNX). Hypothesis: The levels of post-PNX regenerative lung growth and angiogenic gene expression are different between males and females. Methods: We perform left unilateral PNX on male vs. female C57BL6 mice, measure the remaining lung weight, and analyze vascular and alveolar regeneration and angiogenic gene expression using immunohistochemical and molecular biological analysis. Results: Post-PNX increases in the remaining lung weight are lower in the female mice compared to males. Alveolar numbers and blood vessel formation are significantly lower in females compared to males. Proliferation of general capillary EC subpopulations increases more in the male mouse lungs after PNX compared to female mice. Post-PNX increases in the expression of angiogenic genes, VEGFR-2, Tie2, and PDGFB are higher in male mice. Conclusion: Post-PNX vascular and alveolar regeneration is less stimulated in females compared to males. Understanding the sex-dependent mechanism would lead to the development of more specific strategies for lung diseases. This project is supported by R01HL142578 and AHA 967800. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.