Steroid Hormone Dependent Pathogenesis in Vascular Ehlers-Danlos Syndrome

We also found a role for mineralocorticoid receptor signaling with the use of spironolactone, a dual AR and MR antagonist, and finerenone, a specific MR antagonist. Therefore, we employed single nucleus-RNAseq of the descending thoracic aorta to identify the molecular mechanism driving AR, MR, and dual AR/MR protection in VEDS male mice. We discovered AR or MR antagonism normalized expression of dysregulated transcripts in both VEDS endothelial cells (ECs) and vascular smooth muscle cells (VSMCs).

In ECs, components of cell junctions and modulators of cell junction stability were dysregulated while transcripts encoding a contractile VSMC phenotype, integrin signaling, and focal adhesions were modulated in VSMCs.