Proportions of basement membrane proteins in cerebrovascular smooth muscle cells after exposure to hypercapnia and amyloid beta
Proportions of basement membrane proteins in cerebrovascular smooth muscle cells after exposure to hypercapnia and amyloid beta
Vascular basement membranes (BMs), composed of laminins, collagen IV, fibronectin, and perlecan, are secreted by endothelial cells, pericytes, smooth muscle cells (SMCs), and astrocytes. In the brain, amyloid beta (Aβ) is eliminated along cerebrovascular BMs of capillaries and arteries as intramural periarterial drainage (IPAD). Ageing modifies vascular BMs, impairing IPAD and leading to Aβ deposition as cerebral amyloid angiopathy. To better understand the molecular determinants of IPAD in ageing, we quantified the relative abundance of BMs secreted by human-derived cerebral endothelial cells, pericytes, brain vascular SMCs, and astrocytes in vitro. We then assessed BM protein levels in SMCs under hypercapnia (8% CO 2) as a model of vascular ageing, with and without Aβ exposure. Of the four cell types, we found SMCs secreted the highest levels of fibronectin, laminin, and perlecan, whilst pericytes secreted the highest levels of collagen IV. Hypercapnia increased the expression of collagen IV and fibronectin in SMCs but decreased the expression of laminin. The expression of perlecan increased under hypercapnia, but only in the presence of Aβ. This work highlights the varying compositions of vascular BMs and the dynamic differential responses of SMCs to Aβ and hypercapnia, helping to elucidate the age-related changes that impair IPAD in cerebral vessels.
Amyloid beta-Peptides/metabolism, Astrocytes/metabolism, Basement Membrane/metabolism, Collagen Type IV/metabolism, Endothelial Cells/metabolism, Fibronectins/metabolism, Humans, Hypercapnia/metabolism, Laminin/metabolism, Membrane Proteins/metabolism, Muscle, Smooth, Vascular/metabolism, Myocytes, Smooth Muscle/metabolism, Pericytes/metabolism, hypercapnia, intramural periarterial drainage, basement membranes, amyloid beta, cerebral amyloid angiopathy
Dewing, Jennifer M.
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Keable, Abby
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Laslo, Alexandru
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Chinezu, Laura
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Ivanescu, Adrian
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Ratnayaka, J. Arjuna
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Kalaria, Raj
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Slevin, Mark
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Verma, Ajay
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Carare, Roxana O.
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18 April 2025
Dewing, Jennifer M.
868fbf01-7b6e-499f-abf9-47409278373f
Keable, Abby
334f0dca-e41d-4c17-9435-df52bab191b2
Laslo, Alexandru
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Chinezu, Laura
13444259-5716-43b4-92b3-19660971eb8e
Ivanescu, Adrian
7394d999-cdd9-44cd-88d8-e6f8363d81fc
Ratnayaka, J. Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
Kalaria, Raj
80b4b094-c190-49c5-8c6e-ccc69ec2297b
Slevin, Mark
fd726c43-331b-4fe4-9eb1-80913e2f8088
Verma, Ajay
5a207350-0de9-487a-be28-f9eb2f558140
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Dewing, Jennifer M., Keable, Abby, Laslo, Alexandru, Chinezu, Laura, Ivanescu, Adrian, Ratnayaka, J. Arjuna, Kalaria, Raj, Slevin, Mark, Verma, Ajay and Carare, Roxana O.
(2025)
Proportions of basement membrane proteins in cerebrovascular smooth muscle cells after exposure to hypercapnia and amyloid beta.
Cells, 14 (8), [614].
(doi:10.3390/cells14080614).
Abstract
Vascular basement membranes (BMs), composed of laminins, collagen IV, fibronectin, and perlecan, are secreted by endothelial cells, pericytes, smooth muscle cells (SMCs), and astrocytes. In the brain, amyloid beta (Aβ) is eliminated along cerebrovascular BMs of capillaries and arteries as intramural periarterial drainage (IPAD). Ageing modifies vascular BMs, impairing IPAD and leading to Aβ deposition as cerebral amyloid angiopathy. To better understand the molecular determinants of IPAD in ageing, we quantified the relative abundance of BMs secreted by human-derived cerebral endothelial cells, pericytes, brain vascular SMCs, and astrocytes in vitro. We then assessed BM protein levels in SMCs under hypercapnia (8% CO 2) as a model of vascular ageing, with and without Aβ exposure. Of the four cell types, we found SMCs secreted the highest levels of fibronectin, laminin, and perlecan, whilst pericytes secreted the highest levels of collagen IV. Hypercapnia increased the expression of collagen IV and fibronectin in SMCs but decreased the expression of laminin. The expression of perlecan increased under hypercapnia, but only in the presence of Aβ. This work highlights the varying compositions of vascular BMs and the dynamic differential responses of SMCs to Aβ and hypercapnia, helping to elucidate the age-related changes that impair IPAD in cerebral vessels.
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cells-14-00614
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Accepted/In Press date: 16 April 2025
Published date: 18 April 2025
Keywords:
Amyloid beta-Peptides/metabolism, Astrocytes/metabolism, Basement Membrane/metabolism, Collagen Type IV/metabolism, Endothelial Cells/metabolism, Fibronectins/metabolism, Humans, Hypercapnia/metabolism, Laminin/metabolism, Membrane Proteins/metabolism, Muscle, Smooth, Vascular/metabolism, Myocytes, Smooth Muscle/metabolism, Pericytes/metabolism, hypercapnia, intramural periarterial drainage, basement membranes, amyloid beta, cerebral amyloid angiopathy
Identifiers
Local EPrints ID: 502188
URI: http://eprints.soton.ac.uk/id/eprint/502188
ISSN: 2073-4409
PURE UUID: defa40a1-beb4-4f62-b6d2-993edf0cd4cc
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Date deposited: 18 Jun 2025 16:32
Last modified: 22 Aug 2025 02:09
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Contributors
Author:
Jennifer M. Dewing
Author:
Abby Keable
Author:
Alexandru Laslo
Author:
Laura Chinezu
Author:
Adrian Ivanescu
Author:
Raj Kalaria
Author:
Mark Slevin
Author:
Ajay Verma
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