The disease CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a recently identified cause of stroke and vascular dementia. CADASIL is identified by finding mutations in a gene called Notch3, which influences how cells in blood vessels grow and develop.
The research reveals blood vessels in CADASIL patients over-react to the hormone Angiotensin II, part of an important hormonal system that regulates blood pressure. This is an important mechanism by which these gene abnormalities lead to poor blood supply in CADASIL patients.
Angiotensin II, which causes common cardiovascular disorders such as high blood pressure and heart failure, is also abnormal in CADASIL patients.
The study published in this month's edition of the international journal Stroke is the first to provide evidence that blood vessels elsewhere in the body, apart from the brain, in CADASIL sufferers are abnormal in over-constricting in response to the hormone Angiotensin II.
Until now, drugs that help cardiovascular conditions in general, such as aspirin, and tablets to lower blood pressure and cholesterol have been given to CADASIL sufferers. This research suggests that new treatments aimed specifically at blocking the Angiotensin II pathway should be administered.
Professor Donald Singer, Head of Clinical Sciences at the University of Warwick Medical School, said: "By revealing that blood vessels in CADASIL patients over-react to the hormone Angiotensin II the study offers insight into new approaches to prevent stroke and other brain disorders. This new knowledge will lead to more effective drugs to treat this debilitating disease that affects younger people and is associated with progressive dementia, migraine headaches and severe depression. Future studies in are needed of specific treatments aimed at blocking this key hormone."
Previous research into CADASIL has focused on changes in the brain. This new research applied micro-engineering methods to study very small arteries obtained from bikini area tissue samples donated by CASADIL patients and control subjects, to explore why blood vessels may behave abnormally in CADASIL.
In Europe and the United States stroke is the third leading cause of death and the primary cause of physical and cognitive difficulties.
For more information contact: Jenny Murray, Communications Office, University of Warwick, Tel: 247-657-4255, Mobile: 44-787-621-7740 or Professor Donald Singer, University of Warwick Medical School, Tel: 44-247-696-8649, Mobile 44-794-782-0104 or Professor Hugh Markus, St George's Hospital Medical School, Tel: 208-725-2735
The research was supported by the British Heart Foundation, the Atkinson Morley Neuroscience Research Foundation and the Cardiovascular Research Trust.