@article{5bbf206068d44b06acf5181f10ed2887,
title = "Global proteomic analysis of extracellular matrix in mouse and human brain highlights relevance to cerebrovascular disease",
abstract = "The extracellular matrix (ECM) is a key interface between the cerebrovasculature and adjacent brain tissues. Deregulation of the ECM contributes to a broad range of neurological disorders. However, despite this importance, our understanding of the ECM composition remains very limited mainly due to difficulties in its isolation. To address this, we developed an approach to extract the cerebrovascular ECM from mouse and human post-mortem normal brain tissues. We then used mass spectrometry with off-line high-pH reversed-phase fractionation to increase the protein detection. This identified more than 1000 proteins in the ECM-enriched fraction, with > 66% of the proteins being common between the species. We report 147 core ECM proteins of the human brain vascular matrisome, including collagens, laminins, fibronectin and nidogens. We next used network analysis to identify the connection between the brain ECM proteins and cerebrovascular diseases. We found that genes related to cerebrovascular diseases, such as COL4A1, COL4A2, VCAN and APOE were significantly enriched in the cerebrovascular ECM network. This provides unique mechanistic insight into cerebrovascular disease and potential drug targets. Overall, we provide a powerful resource to study the functions of brain ECM and highlight a specific role for brain vascular ECM in cerebral vascular disease.",
keywords = "basement membrane, Cerebrovascular, extracellular matrix, matrisome, proteome",
author = "Alexandra Pokhilko and Gaia Brezzo and Lahiru Handunnetthi and Raphael Heilig and Rachel Lennon and Colin Smith and Allan, {Stuart M.} and Alessandra Granata and Sanjay Sinha and Tao Wang and Markus, {Hugh S.} and Alexandra Naba and Roman Fischer and {Van Agtmael}, Tom and Karen Horsburgh and Cader, {M. Zameel}",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research reported in this publication was primarily supported by a Stroke Association priority programme award in Advancing Care and Treatment of Vascular Dementia (grant reference number 16VAD_04) in partnership with the British Heart Foundation and Alzheimer's Society. KH received funding support from the Alzheimer{\textquoteright}s Society (152 (PG-157); 290 (AS-PG-15b-018); 228 (AS-DTC-2014-017)) and Alzheimer{\textquoteright}s Research UK (ARUK) (ARUK-PG2016B-6). TVA was funded by MRC (MR/R005567-1), BHF (PG/15/92/31813), and Heart Research UK (RG 2664/17/20). SS was also funded by BHF Fellowship (FS/18/46/33663) and the Cambridge BHF Centre for Research Excellence. SMA was funded by MRC, BHF and Leducq Foundation. ZC received funding support from from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking (IM2PACT grant no. 807015 ); from National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC); and from MRC (MC_PC_16034). Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Cader reports personal fees from Eli Lilly, Novartis and grants from Orion, Daiichi Sankyo, and Oxford Science Innovations outside the submitted work. Dr. Cader is Director of Oxford StemTech Ltd and reports personal fees from Eli Lilly, Novartis and grants from Orion, Daiichi Sankyo, and Oxford Science Innovations outside the submitted work. Publisher Copyright: {\textcopyright} The Author(s) 2021. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = mar,
day = "17",
doi = "10.1177/0271678X211004307",
language = "English",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Springer Nature",
}