Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients
| Autor: | Ruifang Lu, Sanjay Sinha, Dieter P. Reinhardt, Shaynah Wanga, Adam Lee Fellows, Marjan Jahangiri, Vivian de Waard, Maarten Groenink, Javier Barallobre-Barreiro, Carlie J.M. de Vries, Barbara J.M. Mulder, Romy Franken, David R. Koolbergen, Rosa Viner, Manuel Mayr, Xiaoke Yin, Qiuru Xing, Aeilko H. Zwinderman, Ron Balm, Ferheen Baig, Philipp Skroblin, Hongorzul Davaapil, Marika Fava |
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| Přispěvatelé: | Sinha, Sanjay [0000-0001-5900-1209], Apollo - University of Cambridge Repository, Graduate School, Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, AGEM - Endocrinology, metabolism and nutrition, Cardiology, Cardiothoracic Surgery, Epidemiology and Data Science, APH - Methodology, Surgery, APH - Personalized Medicine, APH - Aging & Later Life |
| Rok vydání: | 2019 |
| Předmět: |
Proteomics
musculoskeletal diseases 0301 basic medicine Marfan syndrome congenital hereditary and neonatal diseases and abnormalities Glycosylation extracellular matrix Fibrillin-1 Myocytes Smooth Muscle elastin macromolecular substances Vascular Remodeling 030204 cardiovascular system & hematology Marfan Syndrome Extracellular matrix 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Translational Sciences medicine Humans cardiovascular diseases glycoproteins Aorta Glycoproteins chemistry.chemical_classification Extracellular Matrix Proteins Aortic Aneurysm Thoracic biology Chemistry Glycopeptides medicine.disease Elastin Cell biology 030104 developmental biology ComputingMethodologies_DOCUMENTANDTEXTPROCESSING cardiovascular system biology.protein Carrier Proteins Cardiology and Cardiovascular Medicine Glycoprotein |
| Zdroj: | Yin, X, Wanga, S, Fellows, A L, Barallobre-Barreiro, J, Lu, R, Davaapil, H, Franken, R, Fava, M, Baig, F, Skroblin, P, Xing, Q, Koolbergen, D R, Groenink, M, Zwinderman, A H, Balm, R, de Vries, C J M, Mulder, B J M, Viner, R, Jahangiri, M, Reinhardt, D P, Sinha, S, de Waard, V & Mayr, M 2019, ' Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients. ', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 39, no. 9, pp. 1859–1873 . https://doi.org/10.1161/ATVBAHA.118.312175 Arteriosclerosis, Thrombosis, and Vascular Biology Arteriosclerosis, thrombosis, and vascular biology, 39(9), 1859-1873. Lippincott Williams and Wilkins |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Supplemental Digital Content is available in the text. Objective: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-β1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up. Conclusions: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS. |
| Databáze: | OpenAIRE |
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