I have followed a chain of thought and I wonder if there is a connection. What do you think? Do these puzzle pieces fit together or maybe just some of them?
The short version: Some ME patients have POTS. Some POTS patients may have autoantibodies against cavin-1. Cavin-1 is required for the formation of caveolae. Regulation of eNOS within caveolae is an important mechanism. eNOS activation leads to high levels of NO in cells. NO-/HNO can activate TRPA1 receptors. TRPA1 is involved in many mechanisms....for example "TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders."
The long version:
Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome.
Link to picture of caveolae
A newly described protein, cavin-1, also known as polymerase I and transcript release factor, is one of the targets of the autoantibodies in POTS. Cavin-1 is required for the formation of caveolae in all mammalian and plays a critical role in regulating caveolae function in endothelial cells.
Reference: Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome
In terms of endothelial cell function, caveolae function, caveolae are important regulators of vascular tone through modulation of endothelial nitric oxide synthase (eNOS) activity. Specifically, regulation of eNOS within caveolae by the coat protein, caveolin-1 (Cav-1), is an important physiological mechanism for control of vascular reactivity, and this pathway is intimately involved with the progression of pathologies likely through suppression of pro-inflammatory signalling pathways.
The relationship between caveolae and eNOS is one of the cornerstones of caveolae involvement in cardiovascular function. Loss of Cav-1 leads to persistent eNOS activation and high levels of NO in cells through the loss of Cav-1 inhibitory effect on eNOS. The Cav-1/eNOS interaction tonically inhibits eNOS activity resulting in sequestering of eNOS in caveolae and reduced NO production.
Reference: Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation
Link to picture of regulation of eNOS in caveolae
NO-/HNO can increase meningeal blood flow by activating TRPA1 receptors, most likely through stimulation of CGRP release from meningeal afferents. Similar mechanisms may be involved in the pathophysiology of headaches associated with the endogenous NO metabolism.
Reference: Involvement of TRPA1 receptors in meningeal blood flow induced by formation of nitroxyl (NO-/HNO)
Previous posts about TRP channels:
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TRP Ion Channels