Nav: Home

Mice with missing lipid-modifying enzyme heal better after heart attack

May 01, 2017

BIRMINGHAM, Ala. - 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.
-end-
Besides Halade, co-authors are Vasundhara Kain, Ph.D., Kevin A. Ingle and Sumanth D. Prabhu, M.D., UAB Division of Cardiovascular Disease.

Prabhu is director of the UAB Division of Cardiovascular Disease and the UAB Comprehensive Cardiovascular Center. He holds the Mary G. Waters Chair of Cardiovascular Medicine.

University of Alabama at Birmingham

Related Heart Failure Articles:

Transcendental Meditation prevents abnormal enlargement of the heart, reduces chronic heart failure
A randomized controlled study recently published in the Hypertension issue of Ethnicity & Disease found the Transcendental Meditation (TM) technique helps prevent abnormal enlargement of the heart compared to health education (HE) controls.
Beta blocker use identified as hospitalization risk factor in 'stiff heart' heart failure
A new study links the use of beta-blockers to heart failure hospitalizations among those with the common 'stiff heart' heart failure subtype.
Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.
Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.
How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.
Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.
NSAID impairs immune response in heart failure, worsens heart and kidney damage
Non-steroidal anti-inflammatory drugs, or NSAIDs, are widely known as pain-killers and can relieve pain and inflammation.
Heart cell defect identified as possible cause of heart failure in pregnancy
A new Tel Aviv University study reveals that one of the possible primary causes of heart failure in pregnant women is a functional heart cell defect.
In heart failure, a stronger heart could spell worse symptoms
Patients with stronger-pumping hearts have as many physical and cognitive impairments as those with weaker hearts, suggesting the need for better treatment.
Patients with common heart failure more likely to have lethal heart rhythms
New Smidt Heart Institute Research shows that patients with Heart Failure with Preserved Ejection Fraction (HFpEF) are more likely to have lethal heart rhythms.
More Heart Failure News and Heart Failure Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#555 Coronavirus
It's everywhere, and it felt disingenuous for us here at Science for the People to avoid it, so here is our episode on Coronavirus. It's ok to give this one a skip if this isn't what you want to listen to right now. Check out the links below for other great podcasts mentioned in the intro. Host Rachelle Saunders gets us up to date on what the Coronavirus is, how it spreads, and what we know and don't know with Dr Jason Kindrachuk, Assistant Professor in the Department of Medical Microbiology and infectious diseases at the University of Manitoba. And...
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at Radiolab.org/donate.