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Blocking arachidonic acid metabolism (LTB4) heals heart without fibrosis
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Taka
2017-05-07 14:49:36 UTC
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Mice with missing lipid-modifying enzyme heal better after heart attack

Two immune responses are important for recovery after a heart attack — an acute inflammatory response that attracts leukocyte immune cells to remove dead tissue, followed by a resolving response that allows healing.

Failure of the resolving response can allow a persistent, low-grade nonresolving inflammation, which can lead to progressive acute or chronic heart failure. Despite medical advances, 2 to 17 percent of patients die within one year after a heart attack due to failure to resolve inflammation. More than 50 percent die within five years.

Using a mouse heart attack model, Ganesh Halade, Ph.D., and his University of Alabama at Birmingham colleagues have shown that knocking out one particular lipid-modifying enzyme, along with a short-term dietary excess of a certain lipid, can improve post-heart attack healing and clear inflammation. Halade, an assistant professor in the UAB Department of Medicine, hopes that future physicians will be able to use knowledge from studies like his to boost healing in patients after heart attacks and prevent heart failure.

“Our goal is healing, and we are reaching that goal,” he said of efforts in the UAB Division of Cardiovascular Medicine.

Why are lipids and lipid-modifying enzymes important in inflammation and resolving inflammation? Three key lipid modifying enzymes in the body change the lipids into various signaling agents. Some of these signaling agents regulate the triggering of inflammation, and others promote the reparative pathway.

The lipids modified by the enzymes are two types of essential fatty acids that come from food, since mammals cannot synthesize them. One is n-6 or omega-6 fatty acids, and the other type is n-3 or omega-3 fatty acids. The balance of these two types is important.

The Mediterranean diet, with a near balance of omega-3 and omega-6 fatty acids, promotes heart health. The Western diet, with large amounts of omega-6 fatty acids that greatly exceed the levels of omega-3 fatty acids, can lead to heart disease.

The three main lipid-modifying enzymes compete with each other to modify whatever fatty acids are available from the diet. So, Halade and colleagues asked, what will happen if we knock out one of the key enzymes, the 12/15 lipoxygenase?

They reasoned that this would increase the metabolites produced by the other two main enzymes, cyclooxygenase and cytochrome P450 because they no longer had to compete with 12/15 lipoxygenase for lipids to modify. This might be a benefit because those signaling lipids produced through the cyclooxygenase and cytochrome P450 pathways were already known to lead to major resolution promotion factors for post-heart attack healing.

The UAB researchers found that knocking out the 12/15 lipoxygenase and feeding the mice a short-term excess of polyunsaturated fatty acids led to increased leukocyte clearance after experimental heart attack, meaning less chronic inflammation. It also improved heart function, increased the levels of bioactive lipids during the reparative phase of healing, and led to higher levels of reparative cytokine markers. Additionally, the heart muscle showed less of the fibrosis that is a factor in heart failure.

Besides congestive heart failure, persistent inflammation aggravates a vicious cycle in many cardiovascular diseases, including atherogenesis, atheroprogression, atherosclerosis and peripheral artery disease.

Halade says further mechanistic studies are warranted to develop novel targets for treatment and to find therapies that support the onset of left ventricle healing and prevent heart failure pathology.

Halade is corresponding author of the paper, “Interaction of 12/15 lipoxygenase with fatty acids alters the leukocyte kinetics leading to improved post-myocardial infarction healing,” published in Heart and Circulatory Physiology, a journal of the American Physiological Society.

SOURCE: http://www.uab.edu/news/innovation/item/8266-mice-with-missing-lipid-modifying-enzyme-heal-better-after-heart-attack

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Hey morons, wouldn't AKBA do the same? Better yet, why the hell don't yo try repeat your heart attack experiment in EFAD animals which cannot make LTB4? Knock, knock, anybody home?

Taka
Rejected Man
2017-05-08 02:49:47 UTC
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Post by Taka
Hey morons, wouldn't AKBA do the same? Better yet, why the hell don't yo try repeat your heart attack experiment in EFAD animals which cannot make LTB4? Knock, knock, anybody home?
Taka
What are there 2 or 3 people posting and reading this group? For what it's worth I agree fully.

Boswellia (AKBA) is amazing. I wonder whether I should just take a dose all the time as opposed to episodic use. I am just musing on the screen.
Taka
2017-05-08 11:40:56 UTC
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Post by Taka
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Post by Taka
Hey morons, wouldn't AKBA do the same? Better yet, why the hell don't yo try repeat your heart attack experiment in EFAD animals which cannot make LTB4? Knock, knock, anybody home?
Taka
What are there 2 or 3 people posting and reading this group? For what it's worth I agree fully.
Boswellia (AKBA) is amazing. I wonder whether I should just take a dose all the time as opposed to episodic use. I am just musing on the screen.
Low dose aspirin and AKBA, why do we need to take these to keep chronic inflammation at bay ??? And why are the "researchers" wasting taxpayers' money on making LOX-12 or COX-2 knockout mice ??? The answer is - Arachidonic Acid. Much cheaper and straightforward experiment can be done to keep mice in an EFAD (no arachidonic acid) state till they die. Then just look how long they lived and which "chronic" disease they got, bingo! No one is going to pay for such a simple experiment while wasting much more funds on the "high tech" knockouts and inhibitors....

Taka
Taka
2017-05-08 11:45:41 UTC
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Learn some, Jack:

"Omega-6 essential fatty acids are found in abundance in polyunsaturated vegetable oils like sunflower, safflower, soybean, cottonseed, grapeseed and corn. They are also high in nuts like pine, walnuts and brazil as well as seeds like sesame, sunflower and pumpkin. One problem with omega-6 fatty acids is they get converted into arachidonic acid by the body. And arachidonic acid is in turn used to generate pro-inflammatory cells and hormones."

MORE: http://lluniversity.com/nuts-and-oils-why-coconut-and-macadamia-nut-are-king/
Rejected Man
2017-05-08 21:38:07 UTC
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Post by Taka
"Omega-6 essential fatty acids are found in abundance in polyunsaturated vegetable oils like sunflower, safflower, soybean, cottonseed, grapeseed and corn. They are also high in nuts like pine, walnuts and brazil as well as seeds like sesame, sunflower and pumpkin. One problem with omega-6 fatty acids is they get converted into arachidonic acid by the body. And arachidonic acid is in turn used to generate pro-inflammatory cells and hormones."
MORE: http://lluniversity.com/nuts-and-oils-why-coconut-and-macadamia-nut-are-king/
I avoid most of this. Certainly all the refined stuff except what is in with my sardine. That said I eat some sunflower seed, walnuts, sesame, pumpkin seeds and peanuts so I get a dose of omega-6. At least when I do that I get all the associated antioxidants.

I also use butter, cheeses, meat, fish, olive oil, pork fat, chicken fat, chicken, sour cream, coconut and coconut fat as I live on a high fat diet.

Brazil nuts have too much selenium to be safe for this man.

What I found makes a difference is eating too much in the way of peppers, tomato and potato (I limited this one due carbs). Not good, moderation with these is tolerated which is hard which the kitchen garden is in full yield.

I'll take a run toward the setting sun.

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