Efficacy of Antihypertensive Drugs and miR-632 Inhibition on Parietal Remodeling in a Model of Marfan Thoracic Aortic Aneurysm

Background: Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 mutations, leading to elastic fiber disarray and early thoracic aortic aneurysm (TAA) formation. Currently, pharmacological treatments lack specificity and only delay progression. We previously reported a specific TGFβ-driven miR-632 up-regulation in MFS TAA tissues and blood causing smooth muscle cell dedifferentiation and aortic wall degeneration. This study evaluated the effects of three conventional antihypertensive drugs (β-blocker, ACE inhibitor and sartan) on parietal remodeling comparing them with a miR-632 inhibitor in an ex vivo TGFβ –induced model of MFS TAA. Methods and Results: Gene expression and western blot analyses demonstrated that only losartan significantly reduced miR-632 and vascular degeneration markers. Notably, combined treatment with ramipril and carvediol compromised losartan’s efficacy, highlighting the need for careful therapeutic selection. miR-632 inhibitor was the most effective strategy in this ex vivo setting, although further preclinical validation is needed to confirm its therapeutic potential in vivo. Conclusions: Our data emphasize that choosing the right treatment in MFS aortopathy requires understanding its specific impact on cellular pathways. Our findings identify losartan as the most effective standard drug while suggesting miR-632 as a promising future target to stabilize the aortic wall and delay surgery.