Conditional deletion of Rcan1 promotes aortic intramural hematoma that progresses to abdominal aortic aneurysm

Resumen del trabajo presentado a la Elastin, Elastic Fibers & Microfibrils Gordon Research Conference: "Elastic Tissues and Regulation of Growth Factor Signaling in Development, Homeostasis and Disease", celebrada en University of New England (USA) del 30 de julio al 4 de agosto de 2017.Aortic intramural hematoma (IMH), a life-threatening acute aortic disease, is a contained aortic wall hematoma with bleeding within the media but without intimal rupture or flap formation. IMH evolves to reabsorption, dissection, or aortic rupture in the short-term, and to aortic aneurysm or pseudoaneurysm in the long-term. The etiology and the molecular mechanisms underlying IMH are mostly unknown. Angiotensin II (AngII) is a known inducer of experimental IMH and abdominal aortic aneurysm (AAA). We have shown that constitutive deletion of Regulator of calcineurin 1 (Rcan1), a downstream target of AngII, prevents AngII-induced AAA in the mouse. Rcan1 is expressed as two isoforms, Rcan1-1, constitutively expressed in most tissues, and Rcan1-4, which is induced by a wide number of stimuli. To determine the relative contribution of each isoform in the vascular and endothelial compartments to aneurysm development, we have used the CreERT2-Lox system to generate mice with inducible deletion of Rcan1-1, Rcan1-4, or both isoforms specifically in vascular smooth muscle cells (VSMC), in endothelial cells (EC), or ubiquitously. While AngII induced IMH in the ascending aorta (AsAo) after 7 days of treatment in