Molecular Profiling of Vascular Remodeling in Chronic Pulmonary Disease
| Autor: | Holger Eubel, Helge Stark, Gregor Warnecke, Hans-Heinrich Kreipe, Anne Hoefer, Danny Jonigk, Lavinia Neubert, Marius M. Hoeper, Patrick Kuenzler, Mark Kuehnel, Jens Vogel-Claussen, Paul Borchert |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Adolescent Hypertension Pulmonary Inflammation Disease Pathology and Forensic Medicine Pulmonary Disease Chronic Obstructive Young Adult Idiopathic pulmonary fibrosis Humans Medicine Young adult Child Aged Regulation of gene expression Lung business.industry Middle Aged Pulmonary edema medicine.disease Pulmonary hypertension Idiopathic Pulmonary Fibrosis medicine.anatomical_structure Child Preschool Airway Remodeling Pulmonary Veno-Occlusive Disease Female medicine.symptom Transcriptome business |
| Zdroj: | The American Journal of Pathology. 190:1382-1396 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2020.03.008 |
| Popis: | Pulmonary hypertension and pulmonary vascular remodeling (PVR) are common in many lung diseases leading to right ventricular dysfunction and death. Differences in PVR result in significant prognostic divergences in both the pulmonary arterial and venous compartments, as in pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease (PVOD), respectively. Our goal was to identify compartment-specific molecular hallmarks of PVR, considering the risk of life-threatening pulmonary edema in PVOD, if treated by conventional pulmonary hypertension therapy. Formalin-fixed and paraffin-embedded tissues from fresh explanted human lungs of patients with PVOD (n = 19), PAH (n = 20), idiopathic pulmonary fibrosis (n = 13), and chronic obstructive pulmonary disease (n = 15), were analyzed for inflammation and kinome-related gene regulation. The generated neuronal network differentiated PVOD from PAH samples with a sensitivity of 100% and a specificity of 92% in a randomly chosen validation set, a level far superior to established diagnostic algorithms. Further, various alterations were identified regarding the gene expression of explanted lungs with PVR, compared with controls. Specifically, the dysregulation of microtubule-associated serine/threonine kinase 2 and protein-o-mannose kinase SGK196 in all disease groups suggests a key role in pulmonary vasculopathy for the first time. Our findings promise to help develop novel target-specific interventions and innovative approaches to facilitate clinical diagnostics in an elusive group of diseases. |
| Databáze: | OpenAIRE |
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