Exercise and aortic root dilation

[pellicle]

https://pubmed.ncbi.nlm.nih.gov/9854552/

very interesting reading

 

[pellicle]

So I would take this data with a grain of salt, however, if I can avoid calcium channel blockers I will

This approach sounds appropriately cautious

But thanks heaps for posting that, I'm still reading

 

[pellicle]

I'm not a scientist and one can create a hypothesis based on this but this was in-vitro so may not have any applicability to in-vivo human.

reasonable but:

Methods: Porcine aortic segments (n = 8) were pre-incubated in exogenous pancreatic elastase for 24 h prior to culture in standard conditions for 6 days with 10 and 100 micrograms/l amlodipine. Control segments were cultured both with and without amlodipine and without elastase. At the termination of culture MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereological analysis of EVG stained sections.​

​

Results: Gel enzymography demonstrated significantly increased MMP-9 activity in the amlodipine treated segments, median 4.218 vs. 2.809 arbitrary units (p < 0.01) and this elevated activity was reflected in a significant destruction of medial elastin 27.0 vs. 40.5% (p < 0.05).​

​

Conclusion: Therapeutic ranges of amlodipine significantly enhanced elastin degradation and potentiated MMP-9 activity within the aortic organ cultures.​

this is so preliminary and essentially ignores the other tornado of effects in the body (and also as you say, dose).

I recall studies showing that 10 times the leathal dose of warfarin fed to rats that were also injected with huge amounts of vitamin K (so that the warfarin didn't kill them) led to decreased calcification ... this was then touted as evidence that warfarin could lead to bone mass loss in humans (which nobody has been concerned about since 1999).

So I always read studies with a cautious eye.

Great discussion, thanks!!

PS:

My cardiologist indicated that he would rather not pile on the drugs if I have a good chance of controlling BP with one drug given the always increasing chance of side effects with multiple medications.

this is prudent too

 

[HeartofClay]

reasonable but:

Methods: Porcine aortic segments (n = 8) were pre-incubated in exogenous pancreatic elastase for 24 h prior to culture in standard conditions for 6 days with 10 and 100 micrograms/l amlodipine. Control segments were cultured both with and without amlodipine and without elastase. At the termination of culture MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereological analysis of EVG stained sections.​

​

Results: Gel enzymography demonstrated significantly increased MMP-9 activity in the amlodipine treated segments, median 4.218 vs. 2.809 arbitrary units (p < 0.01) and this elevated activity was reflected in a significant destruction of medial elastin 27.0 vs. 40.5% (p < 0.05).​

​

Conclusion: Therapeutic ranges of amlodipine significantly enhanced elastin degradation and potentiated MMP-9 activity within the aortic organ cultures.​

this is so preliminary and essentially ignores the other tornado of effects in the body (and also as you say, dose).

I recall studies showing that 10 times the leathal dose of warfarin fed to rats that were also injected with huge amounts of vitamin K (so that the warfarin didn't kill them) led to decreased calcification ... this was then touted as evidence that warfarin could lead to bone mass loss in humans (which nobody has been concerned about since 1999).

So I always read studies with a cautious eye.

Great discussion, thanks!!

PS:



this is prudent too

Aortic dilation seems to be a disorder of elastin as much as collagen with elastin stores in the body being more preset - enough to last many decades under normal wear and tear. I'm not sure you can build elastin vs. just slow its degradation. I've been frustrated trying to find supplements to help. Taking "elastin" supplements never caught on (likely as a result of sketchy data) vs. collagen supplements which at least have a little clinical support. On a positive note, I did find this on study on Dill Extract. I've purchased a tincture of dill a couple times from Amazon. But just a guess if it works, and if it did, what dosage would be physiologically impactful.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072659/

 

[pellicle]

A

Aortic dilation seems to be a disorder of elastin as much as collagen with elastin stores in the body being more preset

Agreed,its part of a connective tissue disorder. But its complex.

 

[HeartofClay]

A

Agreed,its part of a connective tissue disorder. But its complex.

I wish I understood it more and that there was a magic bullet to reinforce our connective tissue, but it's so multi-factorial and complex as you state. I appreciate this forum, as the pooled knowledge of diagnosis, treatment and recovery is very helpful given the really long-term nature of this process.

 

[pellicle]

Good morning

I wish I understood it more

so too do thousands of researchers working in the area; with PhD's and many years in the area. Worse I think its actually beyond human comprehension because it is (as you say) exactly so multi factor.

but it's so multi-factorial and complex

Interesting snippet of that is that BAV (the connective tissue disorder) has some overlaps with Marfan and of course areas where they differ (interesting). Meanwhile if you have BAV we identify that you're much less predisposed to Coronary Artery Disease (reference).

as it happens as a budding young biochem undergrad (with my BAV as the driver) I saw a movie which summarised what I was to later understand: its all swings and roundabouts. Something that makes something strong makes it brittle.

This scene is a nice "theatric laymans" view of swings and roundabouts.



So my advice is nothing lasts, so "revel in your time"

It won't directly help you, but this guys YouTube channel is filled with some amazing and excellent visualisations of the wonder of molecular biology

https://www.youtube.com/@Clockworkbio

Best Wishes

 

[tjay]

@HeartofClay I don't think you need to look at your situation from a genetic angle, since at 4.0 cm aorta at age 62 you don't seem to have any interesting genetic variant. Plus your current plans to tackle it going forward seem sufficient. That's why I didn't send this link earlier but if you really want to lhave some fun time reading, here's the same:

https://www.valvereplacement.org/threads/question-about-genetic-testing.889515/page-2#post-934940

You don't need this overkill though.

 

[HeartofClay]

@HeartofClay I don't think you need to look at your situation from a genetic angle, since at 4.0 cm aorta at age 62 you don't seem to have any interesting genetic variant. Plus your current plans to tackle it going forward seem sufficient. That's why I didn't send this link earlier but if you really want to lhave some fun time reading, here's the same:

https://www.valvereplacement.org/threads/question-about-genetic-testing.889515/page-2#post-934940

You don't need this overkill though.

Thanks for the link.

 

[HeartofClay]

Good morning



so too do thousands of researchers working in the area; with PhD's and many years in the area. Worse I think its actually beyond human comprehension because it is (as you say) exactly so multi factor.



Interesting snippet of that is that BAV (the connective tissue disorder) has some overlaps with Marfan and of course areas where they differ (interesting). Meanwhile if you have BAV we identify that you're much less predisposed to Coronary Artery Disease (reference).

as it happens as a budding young biochem undergrad (with my BAV as the driver) I saw a movie which summarised what I was to later understand: its all swings and roundabouts. Something that makes something strong makes it brittle.

This scene is a nice "theatric laymans" view of swings and roundabouts.



So my advice is nothing lasts, so "revel in your time"

It won't directly help you, but this guys YouTube channel is filled with some amazing and excellent visualisations of the wonder of molecular biology

https://www.youtube.com/@Clockworkbio

Best Wishes

Cool channel, will check it out. Thanks.