How olive oil and sleep could stave off heart attacks and strokes—new study examines plasma protein's role

September 6, 2018, St. Michael's Hospital
New research from Dr. Heyu Ni, Platform Director for Hematology, Cancer and Immunological Diseases at the Keenan Research Centre for Biomedical Science (KRCBS) of St. Michael's Hospital and his team demonstrates that ApoA-IV is an inhibitory factor for platelets, uncovering why foods high in unsaturated fats may protect against cardiovascular disease. Credit: St. Michael's Hospital

Foods high in unsaturated fats may protect against cardiovascular disease, and new research published today in Nature Communications has uncovered why.

Apolipoprotein A-IV, known as ApoA-IV, is a plasma protein. Levels of ApoA-IV increase after the digestion of foods, particularly foods high in unsaturated fats, such as olive oil. Higher levels of ApoA-IV in the blood have been reported to be associated with lower rates of cardiovascular disease.

New research from the Keenan Research Centre for Biomedical Science (KRCBS) of St. Michael's Hospital demonstrates that ApoA-IV is an inhibitory factor for platelets, which are small blood cells that play a key role in multiple diseases, particularly in bleeding and cardiovascular diseases.

These new findings suggest that ApoA-IV is a blocker of platelet surface glycoproteins GPIIbIIIa (also named integrin αIIβ3). Integrin αIIβ3 is a platelet receptor that is necessary for platelets to clump together in the blood (called platelet aggregation). Platelet aggregation can cause vessel occlusion that blocks , leading to thrombosis, which is the most common cause of mortality and morbidity worldwide.

"Platelet aggregation can save lives, because it can stop bleeding in damaged vessels," said Dr. Heyu Ni, Platform Director for Hematology, Cancer and Immunological Diseases at the KRCBS, who is the principal investigator of this study. "But we usually don't want platelets to block blood flow in the vessels. This is thrombosis, and if vessel occlusion occurs in the heart or brain, it can cause heart attack, stroke or death."

Platelets bind together with a series of connectors. For one platelet to bond to another, the platelet receptor integrin αIIβ3 first binds to fibrinogen—an abundant protein that bridges platelets in blood—and fibrinogen molecules then bind another integrin αIIβ3 on a second platelet. Then fibrinogen and likely also other proteins allow many platelets to bind one another, leading to platelet aggregation.

Examining both lab models and humans, Dr. Ni, who is also a scientist at Canadian Blood Services Centre for Innovation, and his team have shown that ApoA-IV can link to the integrin αIIβ3 and block fibrinogen binding, decreasing platelet aggregation in a vessel. The ApoA-IV protein can also change its shape to accommodate increased blood flow, and become more effective to protect vessels from complete blockage.

"This is the first study to link ApoA-IV with platelets and thrombosis," Dr. Ni said. "With this work, we have also explained why higher levels of ApoA-IV can slow down plaque build-up in blood vessels, known as atherosclerosis, because this process is also related to platelet function."

The researchers also examined ApoA-IV's interaction with food. After every meal, platelets are stimulated, which makes it easier for them to bond together or bond to white blood cells. ApoA-IV increases in circulating blood almost immediately after meals containing unsaturated fats and decreases platelet hyperactivity and bonding, thus reducing the inflammation after meals and the risk of heart attack and stroke.

The study also found that ApoA-IV has its own circadian rhythm. It is most active overnight and least active in the morning.

"Mother Nature wants us to sleep well," Dr. Ni said. "So we are protected by this protein while we sleep, and most likely to experience a cardiovascular event after waking up in the morning."

Dr. Ni and his team are excited about these findings because they show that foods with high unsaturated fats, along with appropriate sleep patterns, create the perfect combination for the protein ApoA-IV to play a positive role in reducing the chances of cardiovascular disease in the form of atherosclerosis, heart attack, or stroke.

This new knowledge has many potential applications, Dr. Ni explained. Future studies will focus on better understanding this protein and how to harness its protective potential to build therapies targeted at and other diseases that arise from activation and aggregation.

Explore further: PCSK9 is a co-activator of platelet function beyond its role in cholesterol homeostasis

More information: Xiaohong Ruby Xu et al, Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis, Nature Communications (2018). DOI: 10.1038/s41467-018-05806-0

Related Stories

PCSK9 is a co-activator of platelet function beyond its role in cholesterol homeostasis

August 28, 2017
PCSK9 is a co-activator of platelet function beyond its role in cholesterol homeostasis, according to research presented at ESC Congress today. The findings suggest that PCSK9 inhibitors, a new class of cholesterol lowering ...

Jamming the signal

April 10, 2018
The formation of blood clots in atherosclerotic arteries results in myocardial infarction and stroke. New research at LMU now demonstrates that low doses of agents developed to treat leukemia can selectively inhibit atherosclerotic ...

Cancer cells metastasize by hitching a ride on platelets

September 8, 2016
Metastasis of cancer cells to sites distant from the primary tumor is the leading cause of cancer-related death, and there is growing evidence that platelets aid the dissemination of cancer cells.

Study shows how dark chocolate may be good for our health—particularly if you are male

December 24, 2012
(Medical Xpress)—Cocoa-rich dark chocolate might help protect against heart disease and stroke, but probably more so if you are a man.

Study may identify new cause of brain bleeds in fetuses and newborns

March 23, 2015
A newly discovered bodily process in mice may explain why some human fetuses who have different antigens than their mothers suffer life-threatening brain bleeds, according to a new study.

Recommended for you

Non-coding genetic variant could improve key vascular functions

November 15, 2018
Atherosclerotic disease, the slow and silent hardening and narrowing of the arteries, is a leading cause of mortality worldwide. It is responsible for more than 15 million deaths each year, including an estimated 610,000 ...

Study of two tribes sheds light on role of Western-influenced diet in blood pressure

November 14, 2018
A South American tribe living in near-total isolation with no Western dietary influences showed no increase in average blood pressure from age one to age 60, according to a study led by researchers at Johns Hopkins Bloomberg ...

Heart failure patients shouldn't stop meds even if condition improves: study

November 13, 2018
(HealthDay)—There's bad news for heart failure patients with dilated cardiomyopathy who'd like to stop taking their meds.

Bypass beats stents for diabetics with heart trouble: study

November 13, 2018
(HealthDay)—People with both diabetes and multiple clogged heart arteries live longer if they undergo bypass surgery rather than have their blood vessels reopened with stents, according to follow-up results from a landmark ...

Kawasaki disease: One disease, multiple triggers

November 12, 2018
Researchers at University of California San Diego School of Medicine, Scripps Institution of Oceanography, and international collaborators have evidence that Kawasaki Disease (KD) does not have a single cause. By studying ...

New treatment significantly reduces cardiovascular events when combined with statins

November 12, 2018
Statins are the most commonly used treatment for cardiovascular disease. Despite reducing certain risk factors, if triglyceride levels remain high with use of statins, there is still a significant risk for heart attack, stroke ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

AlmostClever
1 / 5 (1) Sep 06, 2018
Maybe, it backs off in the morning, readied to clot those injuries, from falling down the craggily slope in front of our cave whilst chasing that breakfast cave rat to ground, before moving on to gathering and pressing the oils from our olive grove.

The shear volume of accommodation nature must provide our proclivity to be, is astounding. If nature was a tennis shoe, it is amazing we are not left with just a tawdry bit of lace left.

How much of this stuff should we chug?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.