Endothelin, Multiple Sclerosis, Systemic Sclerosis, Anti-ETAR AAb, Exosomes and CFS/ME

[SlamDancin]

Again, not antibodies, but this huge study of unexplained OI, which when stressed tested included POTS in some, concluded this;

“CONCLUSIONS: Resting CT-proET-1 and CT-proAVP are increased in orthostatic hypotension”

https://www.ncbi.nlm.nih.gov/m/pubmed/26053073/?i=3&from=orthostatic hypotension endothelin

However not in POTS. So, for people like myself who have orthostatic hypotension but not POTS, Endothelin and nitric oxide look like they would go hand in hand in being elevated. I’m going to get tested for the ETAR antibodies, the test is cheap.

 

[wastwater]

GPR39 is potentially effected in myself,probably lowered

 

[pattismith]

(DPN in Diabetes may be Small Fiber Neuropathy)

Endothelin-1 predicts incident Diabetic Peripheral Neuropathy in Type 2 Diabetes: A cohort study
Feb 2020

Abstract/Excerpt

Introduction
Diabetic peripheral neuropathy(DPN) is a microvascular complication in patients with Type 2 Diabetes(T2D). Apart from hyperglycemia, few modifiable risk factors have been identified. Endothelin-1 is a potent vasoconstrictor peptide, causally implicated for microangiopathy. We investigated whether baseline plasma Endothelin-1 predicted incidence of DPN in a 3-year observational, cohort study.

...

Conclusion
Higher baseline Endothelin-1, blood pressure and diabetes duration were significant and independent predictors for incident DPN. Validation of our findings in independent cohorts and molecular mechanistic studies will help better our understanding on the role of Endothelin-1 in DPN.

 

[pattismith]

A very interesting thing is that Raynaud phenomenon is linked to Systemic Sclerosis, and Erythromelalgia is a possibly associated condition to Raynaud.

In both Raynaud and EM, poor skin capillaries perfusion is noticed, while shunting circulation is either vasoconstricted or dilated..

AT1R and ETAR activating auto-antibodies play a role in SS, so I wonder if they play a role in Raynaud and EM as well.
I am also concerned about the role AT1R antibodies could play in skin cellulite.
Cellulite was associated to polymorphism in the ACE gene, with impaired angiotensin conversion enzyme activity.
This lead to decrease in Angiotensin I and reactive increase in Angiotensin II, and Angiotensin II is an activator of AT1R....
Reduced subcutaneous adipose tissu blood flow and hypoxia has been proposed among cellulite causes, so I wonder if women with cellulite may have some link with AT1R auto-antibodies...I don't find any study yet.

https://en.wikipedia.org/wiki/Cellulite
https://books.google.fr/books?id=Mf...AQ#v=onepage&q="cellulite"angiotensin&f=false
https://europepmc.org/article/med/26970493
https://www.circulationfoundation.o...cular-information/raynauds-systemic-sclerosis

 

[pattismith]

Fibromyalgia versus small fiber neuropathy: diverse keratinocyte transcriptome signature. - Abstract - Europe PMC 2021

Validation of selected candidates in an independent cohort confirmed higher expression of the pro-inflammatory mediators

-interleukin-8,
-C-X-C motif chemokine 3,
-endothelin receptor type A,
-and the voltage-gated sodium channel 1.7

in SFN compared to FMS patients.

We provide a diverse keratinocyte transcriptome signature between SFN and FMS patients, which may hint towards distinct pathomechanisms of small fiber sensitization in both entities and lay the basis for advanced diagnostics.

several studies make the link between endothelin 1 and MMP activation, and also between endothelin 1 and Mast cells degranulation, I just quote one of them:

Stress upregulates arterial matrix metalloproteinase expression and activity via endothelin A receptor activation | American Journal of Physiology-Heart and Circulatory Physiology

Exposure to stress caused a two fold increase in plasma ET-1 levels (P < 0.05), and there was increased ET-1 staining at the tissue level.
Total MMP activity and expression of MMP-2 and MMP-9 were increased in the stress group. ETA receptor antagonism prevented the increase in MMP expression and activation in the stress group.
These results provide evidence that the MMP system is activated before the development of hypertension and ET-1 mediates these early events in vascular remodeling.

 

[pattismith]

• Research Article

  [*]Published: 04 November 2020

Role of central endothelin-1 in hyperalgesia, anhedonia, and hypolocomotion induced by endotoxin in male rats

• Luís Alexandre Lomba,
• Juliana Varella Cruz,
• Letícia Costa Mastrangelo Coelho,
• Mariane Cristina Guttervill Leite-Avalca,
• Diego Correia &
• Aleksander Roberto Zampronio

• Abstract
  
  Sickness syndrome is an adaptive response that can be distinguished by specific signs and symptoms, such as fever and generalized hyperalgesia.
• Endothelin-1 (ET-1) is produced by inflammatory stimuli, including lipopolysaccharide, and involved in the pathogenesis of inflammation and pain by acting through ETA and ETB receptors. ET-1 also induces fever by acting on the central nervous system.
• The present study investigated the role of ET-1 in sickness syndrome responses, including hyperalgesia, anhedonia, and hypolocomotion. Intracerebroventricular ET-1 administration induced mechanical and thermal hyperalgesia in rats, which was ameliorated by the ETA receptor antagonist BQ123 and exacerbated by the ETB receptor antagonist BQ788. A cyclooxygenase blocker did not alter hyperalgesia that was induced by ET-1. Lipopolysaccharide administration induced hyperalgesia, and both BQ123 and BQ788 abolished this mechanical hyperalgesia, but the thermal response was only partially blocked.
• The blockade of ETA receptors in the hypothalamus also abolished lipopolysaccharide-induced mechanical hyperalgesia, and the ETB receptor antagonist did not influence this response. Lipopolysaccharide also induced anhedonia, reflected by lower sucrose preference, and reduced locomotor activity. Both antagonists restored locomotor activity, but only BQ788 reversed the reduction of sucrose preference. These results indicate that ET-1 and both ETA and ETB receptors are involved in various responses that are related to sickness syndrome, including hyperalgesia, anhedonia, and hypolocomotion, that is induced by LPS.
  Hypothalamic ETA but not ETB receptors are involved in mechanical hyperalgesia that is observed during lipopolysaccharide-induced sickness syndrome.