Inhibition of thrombin, an unexplored function of retinoic acid

General Discussion
#1

I thought I posted this one, I guess not.

Inhibition of thrombin, an unexplored function of retinoic acid

Published online 2019
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484212/#:~:text=Thus%2C%20retinoic%20acid%20is%20a,the%20first%20time%20in%20vitro.
Amongst vitamin A and its derivatives, retinoic acid showed the highest inhibition of both the forms of thrombin. Vitamin A and its derivatives also displayed remarkable inhibition of platelet aggregation. This is the first report of vitamin A and its derivatives showing inhibition of thrombin and platelet aggregation in vitro .

The present study opens a window to understand blood coagulation in animals by highlighting the thrombin inhibitory activity of retinoic acid and this further helps us to decipher some key aspects of the process of atherosclerosis.

Inhibition of thrombin and platelet aggregation is an important aspect while considering a therapeutic solution to inhibit blood clotting as a preventive measure in case of medical conditions such as cardiovascular disease, stroke and deep vein thrombosis. Anti-platelet drugs such as aspirin, ticlopidine and clopidogrel are administered in case of arterial thrombotic conditions such as cardiovascular disease and stroke; while anti-thrombin drugs such as heparin, argatroban and hirudin are administered in case of both arterial and venous thrombotic conditions. In the case of venous thrombotic conditions, anti-thrombin drugs are very crucial to prevent clotting and therefore, in the pursuit of novel anti-thrombin drugs, the work presented opens a window on the inhibition of thrombin by naturally-occurring vitamin A. The future pursuit in this direction is to perform experiments to examine the in vivo effects of vitamin A and its derivatives in inhibition of thrombosis, wherein direct thrombin inhibition by vitamin A and its derivatives can be expected to occur in vivo . If vitamin A and its derivatives show promising results towards anti-thrombosis, then, these molecules will be one of the most potent prospective drugs. The work presented in this manuscript also opens up opportunities for researchers to perform experiments on the inhibition of thrombin and platelet aggregation by retinoid molecules from natural sources such as trisporic acid [42], isotretinoin (13-cis-retinoic acid), alitretinoin (9-cis-retinoic acid), etretinate, adapalene etc.

#2

So how does this relate to PFS?
Lets say PFS could be a retinoic acid deficiency, which could be dependant on gut bacterial composition.
Obviously theres some vascular abnormalities with PFS.
I never would have thought retinoic acid could be involved in coagulation.
Also I have a thought on lack of heat generation or certain body parts feeling cold, which could be pretty dangerous.
Ive mentioned retinoic acid playing a role in thermoregulation,
I think the ability to generate heat or even short-term inflammation could be important in combating PFS.

Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling

https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.201700396R

Role of brown adipose tissue in body temperature control

Obviously retinoic acid plays a major role in immunity,
Many studies have focused on RALDH2 expressed in dendritic cells and found that retinoic acid produced by this enzyme plays a crucial key role in IgA production, T cell homing, and regulatory T cell induction in the intestine (31–33).

In the skin as well,

https://stke.sciencemag.org/content/12/590/eaay6954

Finally looking at the androgen Receptor if it truly is overexpressed,
there seems to be a very close relationship between RA and AR with their antagonism and regulation. RA might regulate AR or act upstream of AR, not the other way around when it comes to a hierarchy.

"Surprisingly, androgens can partially compensate for the loss of RA signaling, and we identify a link between the endocrine system and RA signaling"

So idk I think you could make a case for Retinoic acid here.

#3

RA prevents metabolic syndrome and yet accutane patients are more susceptible to develop metabolic syndrome.

While taking vitamin A i have been thinking AR may be lower, so might not benefit finestride people.

#4

I would be sure to separate Accutane from Vitamin A, being that it barely binds to retinoic acid receptors.
Most of Vitamin A’s biological effects are mediated through all-trans retinoic acid and activation of its receptors, not 13-cis (Accutane).

Another point would be a possible scenario where intake of vitamin a isnt the problem, its the conversion to retinoic acid.
If a person where to try to increase their intake of vitamin a through supplements for example, they could also become more susceptible to its toxic effects due to lack of turnover or production of RA.
This is a theory of course.

#5

Another theory is lack of intestinal absorption, but skin retinol would not go so high on accutane, I guess there could be an increased skin requirement for retinol making other organs deficient, but also seems like people have skin issues lacking retinol, classic example people having acne come back after treatment. But it tends to be not as bad as before.

I tend to think about it as an increased breakdown of RA, like in alcoholics. I could be wrong.

I doubt retinol is loaded up doing nothing.