Unravelling the threads of Marfan Syndrome and mitochondrial metabolism

Marfan syndrome (MFS) is a heritable connective tissue disorder primarily caused by pathogenic variants in the fibrillin-1 (FBN1) gene, with early mortality often resulting from aortic complications. In this thesis, I investigate metabolic changes in MFS, highlighting mitochondrial dysfunction as a key factor in worsening aortic pathology. Focusing on the abundant smooth muscle cells (SMCs) in the aorta, I discuss SMC heterogeneity and plasticity to clarify their role in vascular disease. I also assess the impact of a high-fat diet and mitochondrial-targeting drugs in MFS mice, exploring potential ways to alleviate both aortic and also lung pathology. Additionally, I introduce five novel mouse models exhibiting diverse phenotypes to better represent the pleiotropic MFS manifestations. These models provide valuable insights and open up avenues for testing new potential treatments.