ARA-290 / Cibinetide multi-tissue healing

[GlassCannonLife]

I just made a long post on using ARA-290 for endothelial dysfunction on the discord. I thought I might share it here and set this up as a thread for if and when I find more interesting anecdotes. From what I have read, it should be useful for any ischemic tissues, including eg brain and heart.

It seems that most people should give it a go if they can afford it.

When we see the results of @Martin aka paused||M.E. 's tests it will be very helpful as we can then also test dysfunction in ourselves. As I mentioned in another post on here, endothelial dysfunction can be indicated by glycocalyx breakdown, and in fact this can start to perpetuate a vicious cycle. Specifically, please see here:

https://pubmed.ncbi.nlm.nih.gov/29408548/

Dysfunctional endothelial cells are an essential contributor to the progression of diverse chronic cardiovascular, renal, and metabolic diseases. It manifests in impairment of nitric oxide-dependent vasorelaxation, vascular permeability, and leukocytes deterrent. While endothelial glycocalyx is known to regulate these functions, glycocalyx has been shown to be impaired in pathologic settings leading to endothelial dysfunction. Are these findings coincidental or are they indicative of a potential cooperation of the glycocalyx and the endothelium in inducing a dysfunctional phenotype? The main thrust of this overview is to advance a hypothesis on the existence of vicious circle relations between impaired endothelial glycocalyx and endothelial cell dysfunction.

Testing glycocalyx function/endothelial dysfunction is done generally through standard ELISA assays of the following, as stated here:

https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-02219-4

markers of glycocalyx damage (syndecan-1 and hyaluronan), endothelial dysfunction (von Willebrand factor; vWF and vascular cell adhesion molecule; VCAM-1)

These aren't rarely examined markers in research, but I haven't checked what people generally look at clinically.

Anyhow, tying this together with ARA-290, we know that ARA-290 acts on the "innate repair receptor" (IRR), which is a term coined by the scientists that discovered the fragment when studying EPO in healing and the regeneration of various tissues. As stated here:

https://pubmed.ncbi.nlm.nih.gov/29392190/

The innate repair receptor (IRR) is a heteromer of the erythropoietin receptor and the β-common (CD131) receptor, which simultaneously activates anti-inflammatory and tissue repair pathways.

As would make sense, endothelial cells indeed have an erythropoietin receptor (EPOR), as well as CD131. Conceptually then, ARA-290 would seemingly have activity that is also specific to endothelial cells.

One concerning factor is that there may be EPOR downregulation with chronic agonism, as found here in vitro:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587987/

I'm not sure if that aspect of long term treatment has ever been experimentally explored.

This study, however:

https://pubmed.ncbi.nlm.nih.gov/27172159/

Title: ARA290, a Specific Agonist of Erythropoietin/CD131 Heteroreceptor, Improves Circulating Endothelial Progenitors' Angiogenic Potential and Homing Ability

Found that they had improved angiogenesis after injury and found that the endothelial colony forming cells (ECFCs) were attracted to the site of injury. It is so specific actually, that this study from 2021 is using it as an experimental tracer for use in diagnosing cardiac ischemia:

https://ijbms.mums.ac.ir/article_18917.html

Overall, I think it seems quite promising in a general "healing" capacity. I'm not sure if long term dosing is the right choice (receptor downregulation could occur.?), but I will look into this further.