Role of TGF-β Signaling in Remodeling of Non-coronary Artery Aneurysms in Kawasaki diseaseβ.

TitleRole of TGF-β Signaling in Remodeling of Non-coronary Artery Aneurysms in Kawasaki diseaseβ.
Publication TypeJournal Article
Year of Publication2015
AuthorsLee, A, Shimizu, C, Oharaseki, T, Takahashi, K, Daniels, LB, Kahn, A, Adamson, R, Dembitsky, W, Gordon, JB, Burns, JC
JournalPediatr Dev Pathol
Date Published2015 Apr 9
iDASH CategoryKawasaki Disease (DBP1 & DBP4)
Abstract<p>Coronary artery aneurysms (CAA) remain an important complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries. Potentially life-threatening 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. Non-coronary artery aneurysms (NCAA) in extra-parenchymal, muscular arteries occur in a minority of patients with KD who also develop CAA, yet little is understood about their formation and remodeling. We postulated that activation of the transforming growth factor-β (TGF-β) pathway in KD may influence formation and remodeling of aneurysms in iliac, femoral, and axillary arteries, the most common sites for NCAA. We studied a resected axillary artery from one adult and endarterectomy tissue from the femoral artery from a second adult, both with a history of CAA and NCAA following KD in infancy. Histology of the axillary artery aneurysm revealed destruction of the internal elastic lamina and recanalization of organized thrombus, while the endarterectomy specimen showed dense calcification and luminal myofibroblastic proliferation. Immunohistochemistry for molecules in the TGF-β signaling pathway revealed increased expression of TGF-β2, TGF-β receptor 2, and phosphorylated SMAD3. These findings suggest ongoing tissue remodeling of the aneurysms decades after the acute injury and demonstrate the importance of the TGF-β signaling pathway in this process.</p>
Alternate JournalPediatr. Dev. Pathol.
PubMed ID25856633