MedicalResearch.com Interview with:
Dr. Beth Kozel M.D. Ph.D
The Laboratory of Vascular and Matrix Genetics
LASKER CLINICAL RESEARCH SCHOLAR
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Elastin is a protein that allows the blood vessels to stretch and recoil. It is made as a child grows but once the child reaches adolescence, the body stops making elastin. With age, the body slowly begins to lose elastin and blood vessels become less flexible.
In order to study what happens when a vessel has less elastin, we used a mouse that makes half of the normal amount of elastin, the Eln+/- mouse. These mice have higher blood pressure, stiffer blood vessels and decreased blood flow to end organs such as the brain. We then used a blood pressure medication, minoxidil (this same medicine when used in topical form helps hair growth), and treated mice from weaning until 3 months of age. With treatment, Eln+/- blood pressure was lower, the vessels were less stiff and blood flow to the brain increased. That effect remained for weeks after the medication was stopped. Additional studies showed that more elastin was present in the vessel wall after treatment and more than 100 other connective tissue genes were also changed, suggesting vessel remodeling. Minoxidil works by causing cells in the blood vessel to relax, leading to a more open, or dilated artery. When taken chronically, our data suggest that the connective tissue associated with a blood vessel remodels, fixing it in a more open state and allowing better blood flow to the organ on the other side, in this case, the brain.
MedicalResearch.com: What should readers take away from your report?
Response: These findings are important because they suggest that blood flow through narrow, stiff blood vessels such as those in the Eln+/- mouse can be improved by treatment with minoxidil. This treatment has the potential to benefit patients with rare diseases of elastin insufficiency such as Williams Beuren syndrome and familial supravalvar aortic stenosis syndrome, but it may also be of benefit to those with aging related elastin loss.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We are excited by the mouse findings but a clinical trial looking at the effect of minoxidil in human patients with elastin insufficiency is needed. In addition, because minoxidil has some significant side effects, the identification of a vascular specific form of this medication will be a benefit to patients.
MedicalResearch.com: Is there anything else you would like to add?
Response: Improved blood flow might improve stroke and vascular dementia rates for people experiencing reduced elastin due to age or genetic changes.
Am J Physiol Heart Circ Physiol. 2018 Mar 2. doi: 10.1152/ajpheart.00683.2017. [Epub ahead of print]
Minoxidil improves vascular compliance, restores cerebral blood flow and alters extracellular matrix gene expression in a model of chronic vascular stiffness.
Knutsen R1, Beeman SC2, Broekelmann TJ3, Liu D4, Tsang KM4, Kovacs A5, Ye L6, Danback J, Watson A4, Wardlaw A4, Wagenseil J7, Garbow JR8, Shoykhet M9, Kozel BA10.
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