Genes, endothelial function and cerebral small vessel disease in man
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1Clinical Neuroscience, St George's, University of London, Cranmer Terrace, London SW17 ORE, UK. hmarkus@sgul.ac.uk
Insights
Cerebral small vessel disease, a cause of stroke, involves two subtypes: isolated lacunar infarction and ischemic leukoaraiosis. Research suggests endothelial dysfunction and genetic factors play a role, but more studies are needed to confirm risk factors.
Area of Science:
- Neurology
- Vascular Biology
- Genetics
Background:
- Cerebral small vessel disease (CSVD) causes ischemic damage to white matter and deep gray matter nuclei.
- It manifests as focal lacunar infarction and diffuse chronic ischemia (leukoaraiosis).
- Two subtypes are proposed: isolated lacunar infarction and ischemic leukoaraiosis, often linked to hypertension.
Purpose of the Study:
- To explore the underlying mechanisms and potential subtypes of cerebral small vessel disease.
- To investigate the role of endothelial dysfunction and genetic predispositions in CSVD pathogenesis.
- To identify robust and replicable risk factors for CSVD.
Main Methods:
- Review of existing literature on CSVD pathophysiology.
- Analysis of evidence linking endothelial activation and dysfunction to CSVD.
- Examination of genetic association studies, including genes related to the renin-angiotensin system, endothelial nitric oxide, and homocysteine.
Main Results:
- CSVD subtypes may include isolated lacunar infarction (linked to microatheroma) and ischemic leukoaraiosis (linked to diffuse arteriopathy and hypertension).
- Evidence suggests endothelial activation and dysfunction contribute to CSVD.
- Genetic factors, particularly those influencing endothelial function, are implicated, though associations require further validation.
Conclusions:
- Cerebral small vessel disease likely comprises distinct subtypes with different underlying pathologies.
- Endothelial dysfunction and genetic predisposition are significant areas of investigation for CSVD.
- Larger, robust studies are necessary to confirm specific genetic associations and establish definitive risk factors for CSVD.
Abstract:
Cerebral small vessel disease results from ischaemia in the perforating arteries supplying the white matter and deep grey matter nuclei. It results in both focal lacunar infarction and more diffuse areas of chronic ischaemia (leukoaraiosis). Two subtypes may exist. One subtype (isolated lacunar infarction) is associated with single or a few larger lacunar infarcts without leukoaraiosis, and may result from microatheroma in the larger perforating arteries. The second subtype (ischaemic leukoaraiosis) results in multiple small lacunar infarcts with leukoaraiosis secondary to a diffuse arteriopathy affecting the smaller perforating arteries, usually occurring in the presence of hypertension. In this subtype, chronic hypoperfusion and impaired cerebral autoregulation have been reported. A number of lines of evidence support a pathogenic role of endothelial activation and dysfunction. Genetic predisposition has also been implicated. Associations with genes involved in endothelial function, including those regulating the renin-angiotensin system, endothelial nitric oxide and homocysteine levels, have been reported. However, not all results have been replicated and there are few robust replicable associations. Larger studies are required to determine definitively which associations represent important risk factors.
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