• Ying-Ju Lai, Po-Ru Chen, Yen-Lin Huang, and Hsao-Hsun Hsu.
• Department of Respiratory Therapy, Chang Gung University College of Medicine, Tao-Yuan, 33353, Taiwan; Cardiovascular Division, Chang Gung Memorial Hospital, Tao-Yuan, 33353, Taiwan; Department of Respiratory Care, Chang-Gung University of Science and Technology, Chia-Yi, 61363, Taiwan.
• J Formos Med Assoc. 2020 Jan 1; 119 (1 Pt 2): 300-309.

Background/PurposePulmonary veno-occlusive disease (PVOD) is a rare but fatal cause of pulmonary hypertension reported to be linked to mutations of eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4), also known as general control nonderepressible 2 kinase (GCN2). PVOD is difficult to diagnose and often initially misdiagnosed as other types of idiopathic pulmonary arterial hypertension (IPAH). To rapidly and correctly identify PVOD patients and explore the possible pathogenesis, we thoroughly investigated histopathological features and GCN2 protein levels in non-PAH, PVOD and PAH patients.MethodsLung specimens were examined for histopathological changes, including those of pulmonary arteries and veins, by Masson's trichrome, modified Verhoeff's and α-SMA staining in the PVOD, IPAH, and non-PAH groups. GCN2 and α-SMA expression in lung tissue was examined by immunohistochemistry and western blotting.ResultsPVOD and IPAH patients showed significant intimal and medial thickening of muscular pulmonary arteries compared with non-PAH patients. PVOD patients had more prominent intimal and medial thickening of muscular pulmonary veins than the other two groups. Interestingly, specialized muscle bundles surrounding the tunica adventitia of the pulmonary artery and vein were observed in PVOD patients. A significant decrease in GCN2 expression in the PVOD group was confirmed by immunohistochemistry and western blotting.ConclusionOur study is the first to show remarkable histological structures, including the wreath-like arrangement of a hyperplastic muscle bundle in the adventitia of pulmonary arteries, in PVOD patients as a diagnostic clue and to disclose the biological difference between PAH and PVOD in a Taiwanese population.Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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