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Primary
Raynaud's Disease Primary Raynaud's disease (PRD) is characterized by the closing of finger and toe blood vessels, with associated color changes, provoked by cold. However, the mechanism by which cooling causes contraction is not known. Our hypothesis is that the cold-induced contraction that characterizes PRD is the result of increased levels of an enzyme (protein tyrosine kinase, PTK) that is involved in the contractile process. To test this hypothesis we use the perfused microvessel technique to determine the effect of stimulators and inhibitors of PTK on drug- and cooling-induced contraction of small arteries removed from skin biopsies taken from human subjects with and without PRD. We also use a biochemical assay to directly measure PTK activity in skin arteries from control and PRD subjects. The results from these studies will provide insight into the link between an alteration in the enzyme and PRD. In so doing, they will provide information on the detailed biochemical mechanism of cold-induced contraction and how this knowledge can be used in the design of therapeutic strategies to treat PRD. Raynaud’s Phenomenon associated with Scleroderma About 90% of individuals with
scleroderma also suffer from Raynaud’s Phenomenon (RP) characterized by a
sharp overreaction to cold by the blood vessels just below the skin especially
in the hands and feet. Neither the
cause of RP nor the reason for the close association with scleroderma is known.
We believe that RP is caused by abnormalities in the activity of an
enzyme (protein tyrosine kinase, PTK) that plays an important role in
controlling both the growth and contraction of the muscle cells that surround
blood vessels. Other studies have
suggested that the activity of PTK may be elevated in individuals with
scleroderma. We propose that
greater PTK activity in individuals with scleroderma causes them to overreact to
cold compared to normal individuals. The research we are performing tests this idea by measuring
the contraction and PTK activity of tiny blood vessels isolated from the skin of
scleroderma and normal individuals. We
look at the response of these vessels to temperature changes and to substances
that are known to affect the activity of PTK.
The establishment of a link between altered PTK activity and RP in
scleroderma could lead to the development of an effective treatment of RP
associated with scleroderma.
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