Tuesday, August 27, 2013

Clinical questions in Essential Hypertension (Gene basis)

Status of the RET gene in Hypertension induced stroke
Let's be frank about this our current understanding of Hypertension and its various therapeutic intervention is not adequate. Strokes appear to occur in a rampant way and the current treatments  are clearly insufficient.The epidemic of Obesity is complicating our progress even more.  Yes obesity is a clear threat to Hypertension control as fat tissue is known to produce ingredients that worsen our autonomic control of blood pressure (we know for example that Sortilin is expressed in testis muscles and fat).
The point is that we can't predict when the autonomic system protecting the brain may deem that enough elevation of blood pressure is too much to "close" the blood vessel long enough to cause an Ischemic stroke!  We suspect that the up and down of Blood pressures cause damages to blood vessels, possibly contributing to a subsequent weakening of the vessel structure prior to some of the bleeding strokes.  But we have no way of predicting these events or estimating the damages early enough to predict a stroke.  (Are there better Biomarkers out there?
One speculation comes to mind, most of the growth factors of the autonomic system have a cystein block, can deacetylation be an effective prevention?  can we measure these compound as Biomarkers  ? can Interferon be used in the prevention of stroke?
You heard me before about the Wnt and the Notch!
But I am not kidding this is where it is all playing out!
There is a tone to blood vessel that is under autonomic control, not our will...And the closest gene controlling these nerve that we know of is VEGF and RET.  Frankly let's look closely at this RET gene now since we have inhibitors (ie Vandetanib).  One of the side effect of Avastin is high blood pressure, did any one care to measure if those with high blood pressure have elevated or amplification of RET?  This RET is a member of the cadherin family (and the Wnt is not to far as you can see!)...what we need to do is to take a group of willing people with hypertension and test them for level of proteins from the GDNF family, and find new biomarkers! (Neurotensin included of course)
Let's go to work people!

(RET gene is a potential tumor inducer because it interacts with a "wild gene" Grb2)
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