Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH) occurring in a heritable form (hPVOD) due to biallelic inactivating mutations of <i>EIF2AK4</i> (encoding GCN2, general control nonderepressible 2) or in a sporadic form in older age (sPVOD),...
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MDPI AG
2022-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/12/1878 |
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| author | Spiro Khoury Antoine Beauvais Jenny Colas Anaïs Saint-Martin Willer Frédéric Perros Marc Humbert Clarisse Vandebrouck David Montani Thierry Ferreira Fabrice Antigny |
| author_facet | Spiro Khoury Antoine Beauvais Jenny Colas Anaïs Saint-Martin Willer Frédéric Perros Marc Humbert Clarisse Vandebrouck David Montani Thierry Ferreira Fabrice Antigny |
| author_sort | Spiro Khoury |
| collection | DOAJ |
| description | Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH) occurring in a heritable form (hPVOD) due to biallelic inactivating mutations of <i>EIF2AK4</i> (encoding GCN2, general control nonderepressible 2) or in a sporadic form in older age (sPVOD), following exposure to chemotherapy or organic solvents. In contrast to PAH, PVOD is characterized by a particular remodeling of the pulmonary venous system and the obliteration of small pulmonary veins by fibrous intimal thickening and patchy capillary proliferation. The pathobiological knowledge of PVOD is poor, explaining the absence of medical therapy for PVOD. Lung transplantation remains the only therapy for eligible PVOD patients. As we recently demonstrated, respiratory diseases, chronic obstructive pulmonary disease, or cystic fibrosis exhibit lipointoxication signatures characterized by excessive levels of saturated phospholipids contributing to the pathological features of these diseases, including endoplasmic reticulum stress, pro-inflammatory cytokines production, and bronchoconstriction. In this study, we investigated and compared the clinical data and lung lipid signature of control (10 patients), idiopathic PAH (7 patients), heritable PAH (9 <i>BMPR2</i> mutations carriers), hPVOD (10 <i>EIF2AK4</i> mutation carriers), and sPVOD (6 non-carriers) subjects. Mass spectrometry analyses demonstrated lung lipointoxication only in hPVOD patients, characterized by an increased abundance of saturated phosphatidylcholine (PC) at the expense of the polyunsaturated species in the lungs of hPVOD patients. The present data suggest that lipointoxication could be a potential player in the etiology of PVOD. |
| first_indexed | 2024-03-09T17:16:00Z |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T17:16:00Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2f19dd2f4a514ebdae1d8c16080009762023-11-24T13:34:57ZengMDPI AGBiomolecules2218-273X2022-12-011212187810.3390/biom12121878Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive DiseaseSpiro Khoury0Antoine Beauvais1Jenny Colas2Anaïs Saint-Martin Willer3Frédéric Perros4Marc Humbert5Clarisse Vandebrouck6David Montani7Thierry Ferreira8Fabrice Antigny9Laboratoire Cooperatif “Lipotoxicity and Channelopathies-ConicMeds”, Universite de Poitiers, Rue Georges Bonnet, 86073 Poitiers, FranceFacultede Medecine, Universite Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceLaboratoire Cooperatif “Lipotoxicity and Channelopathies-ConicMeds”, Universite de Poitiers, Rue Georges Bonnet, 86073 Poitiers, FranceFacultede Medecine, Universite Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceFacultede Medecine, Universite Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceFacultede Medecine, Universite Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceLaboratoire Cooperatif “Lipotoxicity and Channelopathies-ConicMeds”, Universite de Poitiers, Rue Georges Bonnet, 86073 Poitiers, FranceFacultede Medecine, Universite Paris-Saclay, 94270 Le Kremlin-Bicêtre, FranceLaboratoire Cooperatif “Lipotoxicity and Channelopathies-ConicMeds”, Universite de Poitiers, Rue Georges Bonnet, 86073 Poitiers, FranceFacultede Medecine, Universite Paris-Saclay, 94270 Le Kremlin-Bicêtre, FrancePulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH) occurring in a heritable form (hPVOD) due to biallelic inactivating mutations of <i>EIF2AK4</i> (encoding GCN2, general control nonderepressible 2) or in a sporadic form in older age (sPVOD), following exposure to chemotherapy or organic solvents. In contrast to PAH, PVOD is characterized by a particular remodeling of the pulmonary venous system and the obliteration of small pulmonary veins by fibrous intimal thickening and patchy capillary proliferation. The pathobiological knowledge of PVOD is poor, explaining the absence of medical therapy for PVOD. Lung transplantation remains the only therapy for eligible PVOD patients. As we recently demonstrated, respiratory diseases, chronic obstructive pulmonary disease, or cystic fibrosis exhibit lipointoxication signatures characterized by excessive levels of saturated phospholipids contributing to the pathological features of these diseases, including endoplasmic reticulum stress, pro-inflammatory cytokines production, and bronchoconstriction. In this study, we investigated and compared the clinical data and lung lipid signature of control (10 patients), idiopathic PAH (7 patients), heritable PAH (9 <i>BMPR2</i> mutations carriers), hPVOD (10 <i>EIF2AK4</i> mutation carriers), and sPVOD (6 non-carriers) subjects. Mass spectrometry analyses demonstrated lung lipointoxication only in hPVOD patients, characterized by an increased abundance of saturated phosphatidylcholine (PC) at the expense of the polyunsaturated species in the lungs of hPVOD patients. The present data suggest that lipointoxication could be a potential player in the etiology of PVOD.https://www.mdpi.com/2218-273X/12/12/1878PVODphospholipidslysophosphatidylcholine |
| spellingShingle | Spiro Khoury Antoine Beauvais Jenny Colas Anaïs Saint-Martin Willer Frédéric Perros Marc Humbert Clarisse Vandebrouck David Montani Thierry Ferreira Fabrice Antigny Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease Biomolecules PVOD phospholipids lysophosphatidylcholine |
| title | Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease |
| title_full | Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease |
| title_fullStr | Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease |
| title_full_unstemmed | Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease |
| title_short | Lipidomic Profile Analysis of Lung Tissues Revealed Lipointoxication in Pulmonary Veno-Occlusive Disease |
| title_sort | lipidomic profile analysis of lung tissues revealed lipointoxication in pulmonary veno occlusive disease |
| topic | PVOD phospholipids lysophosphatidylcholine |
| url | https://www.mdpi.com/2218-273X/12/12/1878 |
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