Abstract 300: Targeting IL-1β Protects From Aortic Aneurysms Induced by Disrupted TGFβ signaling in SMCs

Aortic aneurysms represent a life-threatening condition because of the current lack of effective treatment, with therapeutic options limited to emergency surgery. Aneurysm formation is typically associated with extracellular matrix remodeling and persistent inflammation. Although the molecular mechanisms underlying aortic pathology remain largely unclear, TGFβ signaling is unquestionably implied and its downstream target Smad4 showed protective functions for maintenance of aortic walls’ integrity. Using mice with smooth muscle cells (SMCs) specific deletion of Smad4 in the adult (Smad4-SMCiko), developing spontaneous aneurysms, we investigated the molecular mechanisms activated by dysregulation of TGFβ signaling. Structural disarrangement of ascending aorta media in Smad4-SMCiko mice was clearly appreciated early after Smad4 deletion as discrete breaks of elastic lamellae. Interestingly, the islands of damage evidenced in the aorta of Smad4-SMCiko were enriched of immune infiltrate, mainly composed by mon...