Some studies showed that eNOS-derived reactive oxygen species play an important role in atherosclerosis progression and restoration of eNOS functionality by upregulation of GCH1 is a rational therapeutic approach. GCH1 transcription has been shown to be upregulated by cytokines, insulin, statins and ARBs. Could be this the next frontier in treatment of atherosclerosis?
Compounds that enhance the bioavailability of NO certainly are likely candidates to be investigated for treatment and prevention of atherosclerosis. I particularly think (it is an impression without any particular reference to it) that these compounds, if given alone , will not have a clearcut effect. However, they could be important to enhance the effect of other interventions.
Best
Chico
Dear Prof. Francisco,
I agree with you. I think it is necessary to study more the mechanisms of actions of these compounds because the favorable effects that it presents in the setting of atherosclerosis and consequently can bring benefits in the prevention and treatment of coronary artery disease.
GCH1 can promote more synthesis of the eNOS co-factor tetrahydrobiopterin and thus technically can enhance NO bioavailability. However, I believe that there are limits to which upregulation of GCH1 can work. We will soon be submitting a manuscript that has analysed the impact tetrahydrobiopterin synthesis rates on eNOS uncoupling at different levels of endothelial cell oxidative stress.
Dr. Kar thanks for the answer. We will be waiting for the manuscript to better understand the mechanisms involved.
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