Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension
Background/purpose: Pulmonary 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Journal of the Formosan Medical Association |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664619302803 |
| _version_ | 1819057248805060608 |
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| author | Ying-Ju Lai Po-Ru Chen Yen-Lin Huang Hsao-Hsun Hsu |
| author_facet | Ying-Ju Lai Po-Ru Chen Yen-Lin Huang Hsao-Hsun Hsu |
| author_sort | Ying-Ju Lai |
| collection | DOAJ |
| description | Background/purpose: Pulmonary 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. Methods: Lung 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. Results: PVOD 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. Conclusion: Our 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. Keywords: Pulmonary veno-occlusive disease, Histopathological features, Hyperplastic muscle bundle |
| first_indexed | 2024-12-21T13:36:18Z |
| format | Article |
| id | doaj.art-64bbaeafc8a34a5eb747a19000d04cc2 |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-12-21T13:36:18Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-64bbaeafc8a34a5eb747a19000d04cc22022-12-21T19:02:10ZengElsevierJournal of the Formosan Medical Association0929-66462020-01-011191300309Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertensionYing-Ju Lai0Po-Ru Chen1Yen-Lin Huang2Hsao-Hsun Hsu3Department 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, TaiwanDepartment of Respiratory Therapy, Chang Gung University College of Medicine, Tao-Yuan, 33353, TaiwanDepartment of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 10002, TaiwanDivision of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 10002, Taiwan; Corresponding author. Fax: +886 2 23412542.Background/purpose: Pulmonary 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. Methods: Lung 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. Results: PVOD 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. Conclusion: Our 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. Keywords: Pulmonary veno-occlusive disease, Histopathological features, Hyperplastic muscle bundlehttp://www.sciencedirect.com/science/article/pii/S0929664619302803 |
| spellingShingle | Ying-Ju Lai Po-Ru Chen Yen-Lin Huang Hsao-Hsun Hsu Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension Journal of the Formosan Medical Association |
| title | Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension |
| title_full | Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension |
| title_fullStr | Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension |
| title_full_unstemmed | Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension |
| title_short | Unique wreath-like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno-occlusive disease versus pulmonary arterial hypertension |
| title_sort | unique wreath like smooth muscle proliferation of the pulmonary vasculature in pulmonary veno occlusive disease versus pulmonary arterial hypertension |
| url | http://www.sciencedirect.com/science/article/pii/S0929664619302803 |
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