Aortic asprosin overexpression does not ameliorate disease pathophysiology in a murine model of Marfan syndrome

Prithviraj Manohar Vijaya, Shetty, Andrea, Matzen, Susanne, Hille, Sabine, Michalewski, Henrike, Witthaus, Marie, Noormalal, Fady, Marcous, Yousef, Morcos, Tarik, Bozoglu, Wiebke, Sommer, Gregor, Warnecke, Christian, Kupatt, Andreas H., Wagner, Regina, Scherließ, Derk, Frank, Gerhard, Sengle, Oliver J., Müller, Anca, Kliesow Remes

Scientific Reports | 2026

Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 mutations, characterised by aortic aneurysms leading to life-threatening dissections. Asprosin is the C-terminal propeptide of fibrillin-1 that was shown to function as a glucogenic hormone with critical implications in vascular pathology. However, its role in MFS remains unknown. Here, we investigate the effect of asprosin overexpression in vascular smooth muscle cells (VSMCs) and in the Marfan mouse model mgR/mgR via endothelial-targeted transduction by adeno-associated viruses (AAVs). In both human and murine VSMCs, asprosin overexpression did not alter VCAM1 or MMP9 expression, while TNF-α-stimulated asprosin-overexpressing MOVAS cells exhibited reduced IL6 levels. In mgR/mgR mice, asprosin overexpression did not affect aortic diameter or elastin integrity. Molecular analyses revealed no significant change in inflammatory or epithelial-to-mesenchymal transition (EMT) markers at the mRNA or protein level, with VCAM1 and MMP9 remaining unchanged. Together, these findings indicate that asprosin overexpression does not ameliorate the aneurysmal phenotype in MFS.