Researchers at the University of Cambridge have grown miniature blood vessel models in the laboratory to study how damage to the structural support of these vessels can lead to leaks.
These findings shed light on conditions such as vascular dementia and stroke, which are associated with small vessel disease.
The study, published in Stem Cell Reports, also identifies a potential drug target to prevent these leaks and mitigate small vessel disease in the brain.
Background: Understanding Small Vessel Disease
Cerebral small vessel disease (SVD) is a significant contributor to age-related cognitive decline and is responsible for nearly half of dementia cases worldwide.
It also plays a role in one-fifth of ischemic strokes, the most common type of stroke, where a blood clot obstructs blood flow to the brain. SVD primarily affects individuals in middle age, with hypertension and type 2 diabetes as common risk factors.
Some rare genetic forms of SVD can affect individuals in their thirties, sharing similar characteristics with the more common, spontaneous form of the disease.
Scientists at the Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, used skin cell samples from patients with a rare genetic form of SVD caused by a COL4 gene mutation.
These skin cells were reprogrammed into induced pluripotent stem cells, which have the potential to develop into various cell types in the body.
The researchers then used these stem cells to create brain blood vessel cells, establishing a disease model that replicates the defects observed in patients’ brain vessels.
Key Findings: “Disrupted Extracellular Matrix and Leaky Blood Vessels”
The blood vessels in our brain rely on a supportive structure called the extracellular matrix, a network-like scaffold. The COL4 gene is essential for maintaining the health of this matrix.
In the disease model, the researchers observed disruptions in the extracellular matrix, particularly at tight junctions that connect cells. This disruption caused the small blood vessels to become leaky, a hallmark of SVD where blood escapes from vessels into the brain.
The researchers pinpointed a group of molecules known as metalloproteinases (MMPs) as central to the damage observed. MMPs typically play a role in preserving the extracellular matrix but can harm its structure when produced excessively.
To counteract this damage, the team treated the blood vessels with drugs that inhibit MMPs, including an antibiotic and an anti-cancer drug. These drugs successfully reversed the damage and prevented further leakage.
Conclusion: Potential for Future Treatments
While the drugs used in the study have significant side effects and may not be suitable for treating small vessel disease, they demonstrate the potential of targeting MMPs as a strategy to halt the disease’s progression.
The researchers believe that their disease model can be scaled up for testing future drug candidates, offering hope for effective treatments in the future.
If you care about stroke, please read studies about how to eat to prevent stroke, and scientists find a breakfast linked to better blood vessel health.
For more information about health, please see recent studies about how Mediterranean diet could protect your brain health, and wild blueberries can benefit your heart and brain.
The research findings can be found in Stem Cell Reports.
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