title: Role of TGF-β Signaling in Remodeling of Noncoronary Artery Aneurysms in Kawasaki Disease.
abstract: 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. Noncoronary artery aneurysms (NCAA) in extraparenchymal, muscular arteries occur in a minority of patients with KD who also have 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.
authors: 1 Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, La Jolla, CA, USA.
authors: Aaron M
authors: AM
authors: Lee
authors: 1 Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, La Jolla, CA, USA.
authors: Chisato
authors: C
authors: Shimizu
authors: 2 Toho University, Ohashi Medical Center, Tokyo, Japan.
authors: Toshiaki
authors: T
authors: Oharaseki
authors: 2 Toho University, Ohashi Medical Center, Tokyo, Japan.
authors: Kei
authors: K
authors: Takahashi
authors: 3 Department of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Lori B
authors: LB
authors: Daniels
authors: 3 Department of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Andrew
authors: A
authors: Kahn
authors: 4 Department of Cardiothoracic Surgery, Sharp Memorial Hospital, San Diego, CA, USA.
authors: Robert
authors: R
authors: Adamson
authors: 4 Department of Cardiothoracic Surgery, Sharp Memorial Hospital, San Diego, CA, USA.
authors: Walter
authors: W
authors: Dembitsky
authors: 5 San Diego Cardiac Center and Sharp Memorial Hospital, San Diego, CA, USA.
authors: John B
authors: JB
authors: Gordon
authors: 1 Kawasaki Disease Research Center, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, La Jolla, CA, USA.
authors: Jane C
authors: JC
authors: Burns
mesh_terms: D000328:Adult; D000783:Aneurysm / Q000175:diagnosis* / Q000209:etiology* / Q000378:metabolism / Q000601:surgery; D001366:Axillary Artery / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D004691:Endarterectomy; D005260:Female; D005263:Femoral Artery / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D015398:Signal Transduction; D051900:Smad3 Protein / Q000032:analysis; D053781:Transforming Growth Factor beta2 / Q000032:analysis*; D066253:Vascular Remodeling; D055815:Young Adult
chemical_list: D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C509041:TGFB2 protein, human; D053781:Transforming Growth Factor beta2; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Kawasaki disease; aneurysms; axillary artery; endarterectomy; femoral artery; iliac artery