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Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.

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Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients. / Yin, Xiaoke; Wanga, Shaynah; Fellows, Adam Lee; Barallobre-Barreiro, Javier; Lu, Ruifang; Davaapil, Hongorzul ; Franken, Romy ; Fava, Marika; Baig, Ferheen; Skroblin, Philipp; Xing, Qiuru; Koolbergen, David R. ; Groenink, Maarten ; Zwinderman, Aeilko H. ; Balm, Ron ; de Vries, Carlie J.M. ; Mulder, Barbara J.M. ; Viner, Rosa ; Jahangiri, Marjan; Reinhardt, Dieter P. ; Sinha, Sanjay ; de Waard, Vivian ; Mayr, Manuel.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 39, No. 9, 01.09.2019, p. 1859–1873.

Research output: Contribution to journalArticle

Harvard

Yin, X, Wanga, S, Fellows, AL, Barallobre-Barreiro, J, Lu, R, Davaapil, H, Franken, R, Fava, M, Baig, F, Skroblin, P, Xing, Q, Koolbergen, DR, Groenink, M, Zwinderman, AH, Balm, R, de Vries, CJM, Mulder, BJM, Viner, R, Jahangiri, M, Reinhardt, DP, 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

APA

Yin, X., Wanga, S., Fellows, A. L., Barallobre-Barreiro, J., Lu, R., Davaapil, H., ... Mayr, M. (2019). Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients. Arteriosclerosis, Thrombosis, and Vascular Biology, 39(9), 1859–1873. https://doi.org/10.1161/ATVBAHA.118.312175

Vancouver

Yin X, Wanga S, Fellows AL, Barallobre-Barreiro J, Lu R, Davaapil H et al. Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients. Arteriosclerosis, Thrombosis, and Vascular Biology. 2019 Sep 1;39(9):1859–1873. https://doi.org/10.1161/ATVBAHA.118.312175

Author

Yin, Xiaoke ; Wanga, Shaynah ; Fellows, Adam Lee ; Barallobre-Barreiro, Javier ; Lu, Ruifang ; Davaapil, Hongorzul ; Franken, Romy ; Fava, Marika ; Baig, Ferheen ; Skroblin, Philipp ; Xing, Qiuru ; Koolbergen, David R. ; Groenink, Maarten ; Zwinderman, Aeilko H. ; Balm, Ron ; de Vries, Carlie J.M. ; Mulder, Barbara J.M. ; Viner, Rosa ; Jahangiri, Marjan ; Reinhardt, Dieter P. ; Sinha, Sanjay ; de Waard, Vivian ; Mayr, Manuel. / Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2019 ; Vol. 39, No. 9. pp. 1859–1873.

Bibtex Download

@article{ddeb568d09a1402fa46ff3ca04ec12da,
title = "Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.",
abstract = "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. VISUAL OVERVIEW: An online visual overview is available for this article.",
keywords = "Elastin, Extracellular matrix, Glycoproteins, Marfan syndrome, Proteomics",
author = "Xiaoke Yin and Shaynah Wanga and Fellows, {Adam Lee} and Javier Barallobre-Barreiro and Ruifang Lu and Hongorzul Davaapil and Romy Franken and Marika Fava and Ferheen Baig and Philipp Skroblin and Qiuru Xing and Koolbergen, {David R.} and Maarten Groenink and Zwinderman, {Aeilko H.} and Ron Balm and {de Vries}, {Carlie J.M.} and Mulder, {Barbara J.M.} and Rosa Viner and Marjan Jahangiri and Reinhardt, {Dieter P.} and Sanjay Sinha and {de Waard}, Vivian and Manuel Mayr",
year = "2019",
month = "9",
day = "1",
doi = "10.1161/ATVBAHA.118.312175",
language = "English",
volume = "39",
pages = "1859–1873",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.

AU - Yin, Xiaoke

AU - Wanga, Shaynah

AU - Fellows, Adam Lee

AU - Barallobre-Barreiro, Javier

AU - Lu, Ruifang

AU - Davaapil, Hongorzul

AU - Franken, Romy

AU - Fava, Marika

AU - Baig, Ferheen

AU - Skroblin, Philipp

AU - Xing, Qiuru

AU - Koolbergen, David R.

AU - Groenink, Maarten

AU - Zwinderman, Aeilko H.

AU - Balm, Ron

AU - de Vries, Carlie J.M.

AU - Mulder, Barbara J.M.

AU - Viner, Rosa

AU - Jahangiri, Marjan

AU - Reinhardt, Dieter P.

AU - Sinha, Sanjay

AU - de Waard, Vivian

AU - Mayr, Manuel

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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. VISUAL OVERVIEW: An online visual overview is available for this article.

AB - 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. VISUAL OVERVIEW: An online visual overview is available for this article.

KW - Elastin

KW - Extracellular matrix

KW - Glycoproteins

KW - Marfan syndrome

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=85071704004&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.118.312175

DO - 10.1161/ATVBAHA.118.312175

M3 - Article

VL - 39

SP - 1859

EP - 1873

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 9

ER -

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