Laura Yuriko González-Teshima, Keisuke Hakamada, Kozue Murata, Reiko Nakagawa, Shiro Baba, Yujiro Ide, Maiko Okamura, Akio Ikai, Tadashi Ikeda, Kenji Minatoya, Masaya Hagiwara, Masaya Ikegawa, Hidetoshi Masumoto
Kyoto University Graduate School of Medicine. RIKEN Center for Biosystems Dynamics Research. Doshisha University. Shizuoka General Hospital.
Japan
Scientific Reports
Sci Rep 2025; 15:
DOI: 10.1038/s41598-025-25523-1
Abstract
Pulmonary arteriovenous malformations (PAVM) are a major surgical complication of univentricular heart therapy, significantly limiting patient survival. Interruption of hepatic venous drainage into the lungs has been long hypothesized to play a critical role in PAVM development by angiogenesis modulation. To understand human plasma role on PAVM development, we conducted a prospective study analyzing paired plasma samples from superior vena cava (SVC) and hepatic vein (HV) origin from 10 infants with congenital heart disease. Two and three dimensional in vitro arteriovenous models were implemented to compare the angiogenic potential of SVC and HV plasma, alongside untargeted shotgun proteomic profiling. Compared to HV, SVC plasma exhibited a pro-angiogenic profile in vitro. SVC proteome was enriched with pro-angiogenic S100 calcium-binding family proteins (S100A7/A8/A9/P). In contrast, HV plasma had unique expression of actin binding proteins (profilin 1/filamin A/actinin alfa 1), and upregulation of pathways associated with vascular stability and cell adhesion maintenance, suggesting a plausible counteracting role to SVC. Our results emphasize the importance of considering not only angiogenesis, but also extracellular mechano-transduction and vascular tone regulation in PAVM pathogenesis; and highlights the value of in vitro arteriovenous modeling to bridge the gap towards PAVM understanding and advancement of future therapeutical alternatives.
Category
Pulmonary Arteriovenous Malformations
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Mechanical and Computer Models of Pulmonary Vascular Disease and Therapy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes