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Autophagy – Impact on Your Infarct

Autophagy – Impact on Your Infarct

Myocardial Infarction? Autophagy can help with that..

Have you ever wondered if our body has some sort of cleansing system? We are constantly moving organisms, and our cells are constantly growing, dividing, and dying. There is so much movement in our mundane looking bodies. There must be a specific way by which our bodies clean out the “bad parts”, right?

Yep! And researchers have pinned down the process in recent years. They call it “autophagy” – because it is a system for your body to consume (-“phagy”) damaged parts of itself (-“auto”). Autophagy has blown up in popularity over the past few years, and it has for good reason. It is the mechanism by which your body keeps itself young.

Autophagy comes in to clean house

That sounds pretty sweet! And it is. Why do you think its blown up? Because it actually works and is really easy to induce. You just need to not eat for a while. (Not eating also comes with the added benefit of saving some $$$$$.)

Summary

Autophagy is so important in maintain healthy cell function, so why wouldn’t it play a major role in myocardial infarction? Heart attacks damage the heart tissue, so some process has to take place in order to keep things running as smoothly as possible. This week’s article is all about autophagy’s role in heart attacks. Researchers from Beijing took on the task to decode the heart.[1] Feel free to take a look at the article for yourself and follow along. [Click here for the file.]

Xiao-Fang T, Shi-Wei Y, Yu-Jie Z. (2017). Autophagy dysglycemia, and myocardial infarction. International Journal of Cardiology Metabolic & Endocrine 14: 40-44.


After reading the article, I found the most important facts to take away were:

  • Autophagy limits the infarct (dead tissue) size and promotes heart cell survival.
  • When your heart has damage from a lack of blood flow / oxygen, it will actually remodel itself to function for the short-term. However, this “remodeling” becomes harmful in the long run.
  • Dysglycemia (both hypo- and hyper-) are highly correlated with infarction, but we don’t fully understand the underlying mechanisms. 

Background Info

Before we get into the weeds here, we should probably talk about what myocardial infarction is and how it happens. When there is a lack of blood flow to the heart, it starves. Cells start to die when there is a lack of oxygen. We call this lack of oxygen flow “ischemia.” This usually happens as a result of atherosclerosis, which is the hardening of the artery wall from plaque build-up.[2]

 

Atherosclerosis (build up of plaque) causes ischemia and infarction


When plaque builds up, I’m sure you can see how this causes blockage of blood to your heart. All of the gunk sitting in your artery prevents blood flow (and thus oxygen) from reaching heart tissue. That’s when the cells starts to die off. When your heart develops dead tissue, it starts to go through emergency mechanisms to still be able to supply blood to the rest of the body.

What about autophagy?

But what does autophagy have to do with all of this heart stuff? We’ll get into that. Right now, let’s talk about what it is. Autophagy is the microscopic cleansing system of the body. It helps keep cells alive through metabolism of damaged and oxidized organelles.[1] If there are too many damaged things, like mitochondria, then the cell will die via apoptosis.[3] Thus, autophagy prevents against this cell death. It will signal a sweep of your entire cell to do some “spring cleaning” so that it never gets to the detrimental point of death.

You induce autophagy through physiological stresses such as starving. When you fast for prolonged periods of time, your body will enter this salvaging state to keep you alive. It supplies nutrients to the body – mainly essential amino acids for protein / enzyme synthesis.However, autophagy can be taken too far. “Excess autophagy can destroy essential cellular components and lead to cell death.”[1] So, the very same mechanism that allows for cell survival is the one that can cause cell death. There is a fine balance. This makes sense because your body is breaking down the broken parts of the cell first, and then it will start breaking down perfectly functioning organelles if it becomes too energy-deprived.

 

Your body breaks down broken parts of cells through autophagy


So we can see why autophagy is good in general – for the whole body to appreciate. But it also has great potential for targeted healing, like after a heart attack or during heart ischemia. Maybe if we can repair the cells through clearing out the damaged parts, we can save the tissue from dying off fully. That was the premise of this article.

Autophagy in mycardial infarction

Something I found very interesting was what happens after you experience a heart attack or major heart tissue death. Your heart will actually start to remodel itself.[1] It will make adaptations to the structure to make sure it can still do its job of pumping blood to the rest of the body. That seemed so odd to me, but apparently, it is a perfectly natural occurrence.

Even though it does this for short-term relief, it actually degrades the heart with time. Maybe there is a way to prevent this remodeling from getting out of hand. That’s what autophagy is there for – it regulates how the cells function and what pathways they decide to take. 

Because heart cells are so specialized, they actually don’t divide and proliferate.[4] They are what we would call “terminally differentiated.” So, because they can’t reproduce new heart cells, autophagy plays an essential role in keeping heart tissue alive.

mTOR Pathway

mTOR is the abreviation for the “mammalian target of rapamycin.” This is a little confusing because rapamycin is a drug that inhibits mTOR.[5] It seems as if they named the pathway after they knew what the drug binds to. Also, I through the picture in here just to show you how complex this is. Don’t actually try to understand it…

 

mTOR signaling pathways...


Anyway, the mTOR pathway is involved in cell growth, metabolism, proliferation and survival.[6] When this pathway is suppressed, cell growth no longer happens. It is only then that autophagy can occur. Autophagy is the body breaking down itself (mainly the dysfunctional pieces) so it can use those parts in other places. If mTOR is activated, then no breaking down will occur – only proliferation will. If mTOR is inhibited, then the body is able to break down the bad parts of the cell for other use.[1][6]

This article found that inhibition of mTOR directly affected myocardial remodeling. When mTOR is inhibited (and thus autophagy can kick into gear), it prevents this dangerous remodeling and limits the dead tissue size.[1][7] aThat leads to the wonder if inhibiting mTOR can play a therapeutic role in keeping heart health.

However great this may seem, autophagy can be taken too far (as stated above). Upregulation of autophagy leads to excessive heart cell death if over done.[1] This makes perfect sense because autophagy is the breaking down of cells. What happens when all the “bad” parts of the cells are broken down? Autophagy will then lead to the breakdown of healthy organelles. Thus when autophagy is taken to an extreme, it can actually make the myocardial infarction worse.

It is a very fine balance – just like with most things in life. But the researchers concluded that “autophagy has a cardioprotective effect during MI [myocardial infarction] according to the reports.”[1]

Dysglycemia

This seemed to be a major topic with this paper, but to be honest, I did not get much out of it. They simply go through the claims that hyperglycemia (too high of blood sugar) is correlated with a higher rate of mortality following myocardial infarction. They also go through how hypoglycemia (too low of blood sugar) is also problematic. However, in this scenario they do not find conclusive evidence that this directly leads to heart failure.

“Hypoglycemia… was not an independent risk factor for future morbidity or mortality in patients with type 2 diabetes and MI.”[1] .sd

They also claim earlier on that lowering the amounts of ATP (energy from the cascading metabolism of food) leads to autophagy – which is cardioprotective. That is why fasting induces autophagy. But extending this idea to hypoglycemia would suggest that lower blood sugar is a good thing. This state will lead to less ATP production. But I am sure it is one of those balancing acts. If it is too low, then autophagy will start and be taken too far.

What I do know from this article is that having metabolic problems (like hyper- / hypo- glycemia) leads to higher rates of heart fatalities. And in classic researcher fashion, they say the exact mechanisms for these processes are not fully understood. So, we just see a correlation, but we don’t really know what is going on here. Not to blame the researchers at all! Science just hasn’t progressed to that point yet.

Yes, more research in these areas is needed! Classic.

Summary

  • Autophagy limits the infarct (dead tissue) size and promotes heart cell survival.
  • When your heart has damage from a lack of blood flow / oxygen, it will actually remodel itself to function for the short-term. However, this “remodeling” becomes harmful in the long run.
  • Dysglycemia (both hypo- and hyper-) are highly correlated with infarction, but we don’t fully understand the underlying mechanisms.

References:

[1] Xiao-Fang T, Shi-Wei Y, Yu-Jie Z. (2017). Autophagy dysglycemia, and myocardial infarction. International Journal of Cardiology: Metabolic & Endocrine 14: 40-44.

[2] Conti CR, Mehta JL. (1987). Acute myocardial ischemia: role of atherosclerosis, thrombosis, platelet activation, coronary vasospasm, and altered arachidonic acid metabolism. Circulation 75(6 Pt 2): V84-95.

[3] Elmore A. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology 35(4): 495-516.

[4] Paradis AN, Gay MS, Zhang L. (2014). Binucleation of cardiomyocytes: the transition from a proliferative to a terminally differentiated state. Drug Discovery Today 19(5): 602-609.

[5] Li J, Kim SG, Blenis J. (2014). Rapamycin: one drug, many effects. Cell Metabolism 19(3): 373-379.

[6] Laplante M, Sabatini DM. (2009). mTOR signaling at a glance. Journal of Cell Science 122(20): 3589-3594.

[7] Nakai A, Yamaguchi O, Takeda T, et al. (2007). The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nature Medicine 13: 619-624.

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