UC San Diego

Coronary artery aneurysms remain a life-threatening complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries (1). Potentially life-threatening coronary artery aneurysms (CAA) develop in 25% of untreated children and 5% of children treated with high dose intravenous immunoglobulin during the acute phase of the self-limited vasculitis (2). Non-coronary artery aneurysms (NCAA) in extra-parenchymal, muscular arteries occur in a minority of patients with KD (2%) who also develop coronary artery aneurysms (CAA) (3, 4), yet little is understood in their formation and remodeling. We postulated that activation of the transforming growth factor TGF beta pathway may influence formation and remodeling of aneurysms in iliac and axillary arteries in KD, the two most common sites for NCAA. We studied the resected axillary artery from one adult and endarterectomy tissue from the iliac artery from a second adult, both with a history of CAA and NCAA following KD in infancy. Histology revealed destruction of the internal elastic lamina with myofibroblastic luminal proliferation, organized thrombus, and recanalization of the axillary artery aneurysm and organized thrombus with dense calcification in the endarterectomy specimen. Immunohistochemistry for molecules in the TGF[beta] signaling pathway revealed increased expression of TGF[beta]2, TGF[beta] receptor, and phosphorylated SMAD3. These findings suggest on-going tissue remodeling of the aneurysms decades after the acute injury and demonstrate the importance of the TGF[beta] signaling pathway in this process