EFEMP2 and Ascending tubular aorta aneurysm: Fibulin-4-deficient mouse models develop ascending aortic aneurysms in association with loss of connections between the elastic fibers and VSMCs, and secondary upregulation of angiotensin II signaling [260,261]; this process was shown to depend on increased sensitivity of fibulin-4-deficient VSMCs to mechanical stretch, which causes an upregulation of thrombospondin-1—a matrix glycoprotein that negatively regulates cell adhesion and positively regulates both angiotensin II and TGF-β signaling [261].