Decreased smooth muscle cells and fibrous thickening of the tunica media in peripheral pulmonary artery stenosis in Alagille syndrome

• Published in: Cardiovascular pathology 2025-01, Vol.74, p.107677, Article 107677
• Main Authors: Ogawa, Yosuke, Yamamoto, Amane, Yamazawa, Sho, Ikemura, Masako, Hirata, Yasutaka, Inuzuka, Ryo
• Format: Article
• Language: English
• Subjects: Alagille syndrome; Alagille Syndrome - complications; Alagille Syndrome - genetics; Alagille Syndrome - pathology; Autopsy; Fatal Outcome; Fibrosis; Heart Failure - etiology; Heart Failure - pathology; Humans; Infant; JAG1; Jagged-1 Protein - genetics; Male; Muscle, Smooth, Vascular - pathology; Mutation; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; NOTCH signaling; Peripheral pulmonary artery stenosis; Pulmonary Artery - pathology; Serrate-Jagged Proteins; Smooth muscle cells; Stenosis, Pulmonary Artery - diagnostic imaging; Stenosis, Pulmonary Artery - etiology; Stenosis, Pulmonary Artery - genetics; Stenosis, Pulmonary Artery - pathology; Tunica Media - pathology
• ISSN: 1054-8807; 1879-1336; 1879-1336
• DOI: 10.1016/j.carpath.2024.107677

•We showed the details of the pathology of pulmonary arteries in Alagille syndrome.•Alagille syndrome presents with hypoplasia and wall thickening of pulmonary arteries.•The lesions are characterized by a reduction in smooth muscle cells.•In contrast, the intrapulmonary arteries remain intact.•These findings support the superiority of surgical pulmonary artery reconstruction. Alagille syndrome is caused by mutations in genes involved in NOTCH signaling, specifically JAG1 and NOTCH2, and is associated with a high rate of peripheral pulmonary artery stenosis. In this study, we report the case of an infant with Alagille syndrome caused by a JAG1 mutation, who succumbed to acute exacerbation of right heart failure due to severe peripheral pulmonary artery stenosis. The autopsy revealed that the peripheral pulmonary arteries were significantly stenosed, exhibiting hypoplasia and thickened vessel walls. Histological examination of the pulmonary artery walls showed a decrease in smooth muscle cells in the tunica media and an increase in collagen and elastic fibers, although the intrapulmonary arteries were intact. These findings are important for understanding the pathogenesis of Alagille syndrome and developing treatment strategies for peripheral pulmonary artery stenosis.