The aorta in Marfan syndrome - from molecular mechanisms to mechanobiological dysfunction - PubMed
2 days ago
- #Aortic Disease
- #Marfan Syndrome
- #Mechanobiology
- Marfan syndrome (MFS) is an autosomal dominant disorder affecting cardiovascular, musculoskeletal, and ocular tissues, with thoracic aortic dissection being a major cause of premature death.
- MFS is caused by pathogenic variants in the FBN1 gene, which encodes fibrillin-1, a glycoprotein important for elastic fiber organization and smooth muscle cell mechano-sensing.
- Despite 35 years since the discovery of FBN1 variants, links between genetic variants and thoracic aortic disease remain incomplete, and definitive treatments are still lacking.
- The review focuses on advances in understanding aortic disease progression in MFS from genetics, histology, mechanobiology, and biomechanics, using mouse models with genetic modifications and pharmacological treatments.
- MFS leads to hundreds of differentially expressed genes in the aorta, which need categorization as protective compensations, pathologic consequences, or neutral changes to guide therapy.
- Data-informed computational models are promising for integrating multimodal data to understand molecular and cellular drivers of disease progression and improve therapies.