Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm

Pericytes exhibit progenitor cell-like qualities and associate with the vasa vasorum-vital microvessels nourishing larger arteries and veins. How pericytes change in human ascending thoracic aortic aneurysm (ATAA) remains unknown. Here, we used the public single-nuclei sequencing data to reveal a contractile phenotype transition of pericytes in human ATAA specimens. In addition, we found that a protective factor, fibroblast growth factor 2 (FGF2), is decreased in the aortic adventitia of both male and female patients with ATAA and impacts pericytes. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic phenotype via MAPK and PI3K-AKT signaling pathways. These findings suggested the latent engagement of pericytes in ATAA, providing insights that could guide the development of new therapies against aortic disease.<b>NEW & NOTEWORTHY</b> Here, we revealed that pericytes transition into a contractile phenotype in human ATAA. We demonstrated that FGF2 maintained pericytes in a less contractile and high angiogenic stage via MAPK and PI3K-AKT signaling pathway, whereas we found FGF2 is decreased in the aortic adventitia of patients with ATAA. Our findings suggest how growth factor deficiency in the microenvironment affects pericytes during ATAA, offering leads for potential new therapies for aortic diseases.