We previously demonstrated that mice with a systemic 75% reduction of fibulin-4 expression (fibulin-4R/R) share key features with the human disease phenotype, including aortic aneurysm formation, aortic valve disease, increased transforming growth factor beta (TGF-β) signaling, and impaired cardiac function15,16. This evidence concerns the gene EFEMP2 and aortic valve disorder.