tirsdag den 24. december 2013

The NO/ONOO cycle - disrupted endothelial caveolae?

Given the focus on endothelial dysfunction (read previous posts) perhaps it is time to take another look at Martin Palls old hypothesis about the NO/ONOO cycle:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome as a NO/ONOO- Cycle Disease

Nitric oxide synthase partial uncoupling as a key switching mechanism for the NO/ONOO– cycle

Martin Palls NO/ONOO- cyklus (på dansk/in Danish)

And his latest paper:

The NO/ONOO-Cycle as the Central Cause of Heart Failure

..if there is a peroxynitrite (ONOO- ) problem in ME/CFS – do ME/CFS patients have disrupted endothelial caveolae – as in this paper?

Peroxynitrite Disrupts Endothelial Caveolae Leading to eNOS Uncoupling and Diminished Flow-Mediated Dilation in Coronary Arterioles of Diabetic Patients:

  • Peroxynitrite (ONOO) contributes to coronary microvascular dysfunction in diabetes mellitus (DM).
  • NO-mediated coronary flow-mediated dilatation (FMD) was significantly reduced in DM patients, which was restored by ONOO scavenger.
  • The researchers propose, that ONOO selectively targets and disrupts endothelial caveolae, which contributes to NO synthase uncoupling, hence reduced NO-mediated coronary vasodilation in DM patients.

…and may an ONOO scavenger help ME/CFS patients?

(Remember: Flow-mediated dilatation (FMD) is a test for assessing endothelial dysfunction, and a study, Large and small artery endothelial dysfunction in chronic fatigue syndrome, showed FMD was significantly lower in ME/CFS patients.)

Some ME/CFS patients say vitamin B12 (cobalamin) helps, and others say it makes no difference. I do not know what to believe, but something I do know, is that the biochemistry behind this is very complicated. I found this paper: 

And then there is folic acid and eNOS activity: 

Folic Acid Reverts Dysfunction of Endothelial Nitric Oxide Synthase

...I fear that vitamins alone can't fix the broken cycle in ME/CFS, but let us hang in there and follow the research about it!!! 

I do believe we are getting closer to answers and a treatment!

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