NIH Research Festival
FARE Award Winner
Aging is associated with increased stiffness of the central vasculature as well as endothelial dysfunction that represents a pathological state where the capacity of the endothelium to dilate blood vessels decreases in response to physical and chemical stimuli. The study stems from the observation that mice deficient of Vav1 expression exhibits dilated blood vessels. Although Vav1 has been reported to be expressed in endothelium, its function remains unclear. We recently discovered that the reduced eNOS activity and increased stiffness in aged mice aorta is due to the accumulation of Vav1. This is due to a decline in the Sirt1 deacetylase level which results in increase eNOS acetylation, reduced S1177 phosphorylation, and thus, attenuates eNOS activity. Our findings suggest that Vav1 promotes the endothelial dysfunction associated with aging, independently of other known cardiovascular risk factors. These findings provide a molecular mechanism of age-associated endothelial dysfunction mediated by Vav1, which provides a target for future development of medical intervention strategies for endothelial dysfunction in the elderly.
Scientific Focus Area: Cell Biology
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