Proteomic analysis of primary human microvascular endothelial cells (HMVECs) stimulated for 24 h with either 50 ï�g/mL recombinant Fibrillin-1 C-terminal fragment or 25 ng/ml VEGF-A compared to unstimulated cells.

ABSTRACT: Mutations in the fibrillin-1 gene result in cardiovascular, ocular, and skeletal abnormalities in Marfan syndrome. Here we show that a fibrillin-1 mutation also alters the neovessel formation. In the mouse retina vascularization model, fibrillin-1 is detected at the basement membrane underlying the angiogenic front and around arterioles. In Fbn1C1041G/+ mice, a model of Marfan disease, the microvasculature is altered at these sites. At the front, endothelial tip-cell sprouting and branching are decreased, and we show that mutant fibrillin-1 delays angiogenesis by affecting Notch signalling. Supplying the growing vasculature of Fbn1C1041G/+ mice with a C-terminal fragment of fibrillin-1 corrects all defects. In vitro, the C-terminal fragment of fibrillin-1 also displays pro-angiogenic activities on microvascular endothelial cell. Our data establish that fibrillin-1 performs essential functions in microvessel formation and integrity and that mutant fibrillin-1-induced defects can be rescued pharmacologically.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Microvascular Endothelial Cell

SUBMITTER: Dupuy Jean-William  

LAB HEAD: Elisabeth Genot

PROVIDER: PXD029834 | Pride | 2023-05-31

REPOSITORIES: Pride