Fibroblast SPP1 mediates ECM deposition and inhibits SMC contractility in MFS aortic aneurysm

Mutations in the Fbn1 gene cause Marfan Syndrome (MFS) and are associated with excessive transforming growth factor beta (TGF-β) signalling activation, which contributes to extracellular matrix (ECM) homeostasis disruption, thoracic aortic aneurysm (TAA) and dissection development. In this study, we aimed to explore the underlying events contributing to ECM metabolism imbalance and TAA and dissection formation in MFS. We performed sequencing analysis and investigated differentially expressed genes as well as cellular communication using CellChat. Fourteen ECM-related differentially expressed genes (DEGs) were identified. Among the 14 genes, secreted phosphoprotein 1 (Spp1) was involved in multiple pathological processes. We then stimulated primary mouse perivascular fibroblasts and aortic SMCs with recombinant Spp1 and recorded increased collagen expression in fibroblasts and decreased expression of Acta2 and Tagln in SMCs. We also investigated SPP1 levels in healthy controls and patients with TAA and found that elevated SPP1 levels were associated with an increased risk of TAA. Our results have indicated that Spp1 regulates ECM changes in fibroblasts and SMCs contractility during TAA. We believe that our study makes a significant contribution to the literature because our results suggest that Spp1 may serve as a potential target for TAA treatment.