Scientific title:
Disintegration of the cerebral matrisome: a central mechanism leading to small vessel disease and vascular cognitive impairment
University of Edinburgh
Principal investigator:
Professor Karen Horsburgh
Grant value:
Research ID:
TSA PPA 2016/02
Research area:
Start date:
Monday 1 January 2018
End date:
Saturday 31 December 2022
4 years
Year awarded:


Cerebral small vessel disease (SVD) affects the small blood vessels in the brain, so they become abnormal and do not regulate blood flow properly to the brain. SVD is a major cause of stroke and vascular dementia, and there are no good treatments because we don't fully understand what causes it.

What is the aim of this project?

This research programme aims to develop new disease models which may be used to better understand what causes SVD, develop possible treatment and approaches, and provide a platform for future studies to screen new drugs that might be useful in treatment.

The research will focus on a part of the brain called the neurovascular unit, which is made of different types of brain cells. This unit controls the blood supply to brain cells, ensuring there is sufficient ‘fuel’ for normal cell function. The brain cells and blood vessels are supported by a scaffold called the extracellular matrix.

New evidence suggests that risk factors for SVD (genes, high blood pressure) may result in damage to the matrix. Professor Horsburgh and colleagues found that mutations in the gene, COL4A1, which encodes a protein that is a major component of the matrix, leads to increased risk of stroke.

What will happen during the project?

The research will use an animal model that has a COL4A1 mutation and develops strokes similar to patients, in order to study SVD and stroke onset and progression. Molecular changes that occur during disease development from the earliest stages will also be determined. These molecular changes will be investigated further in human cell models, with the aim of identifying if they can be modified and to establish whether they are potential treatment targets. For this, stem cells generated from patients with COL4 gene mutations will be used to make the cells of the neurovascular unit, which then form a new human platform to investigate the neurovascular unit and test drugs.

Find out what we think about using animals in research.

What difference could this research make?

This research programme could substantially increase our understanding of how SVD develops, leading to new ways to investigate SVD and test drugs which may help treat it.