The protein is called apolipoprotein A-IV (ApoA-IV), and evidence already exists to suggest that higher blood levels of it are linked to lower risk of cardiovascular diseases.
Now, for the first time, scientists at St. Michael’s Hospital in Toronto, Canada, have shown that ApoA-IV stops blood platelets forming into blood clots.
They also suggest that ApoA-IV could work to slow down inflammatory conditions — such as those that gradually clog arteries — without hampering the “platelet aggregation” that stops bleeding.
They report their findings in a study paper that now features in the journal Nature Communications.
“Platelet aggregation can save lives,” says senior study author Heyu Ni, a platform director in the St. Michael’s Hospital Keenan Research Centre for Biomedical Science, “because it can stop bleeding in damaged vessels.”
“But,” he adds, “we usually don’t want platelets to block blood flow in the vessels.” If the blocked blood vessel is in the heart or brain, for instance, “it can cause heart attack, stroke, or death.”
Atherosclerosis and thrombosis
As Ni and his colleagues note in their study paper, “Thrombotic disorders, such as heart attack and stroke, are the leading causes of mortality and morbidity worldwide.”
In the United States, approximately 790,000 people have a heart attack and 795,000 people have a stroke every year.
Most heart attacks and strokes are due to atherosclerosis, a disease in which plaques build up in the lining of arteries that deliver oxygen- and nutrient-rich blood to the heart and the rest of the body.
These plaques consist of substances that are found in blood, such as calcium, fats, and cholesterol.
The exact causes of atherosclerosis are unclear, but there is evidence to suggest that it is complex, starts early in life, and speeds up with age.
It could be that plaques form at sites of damage in the artery, and — as they harden and thicken with time — they narrow the blood vessel.
Eventually, the plaque can burst, causing platelets to clump together into a blood clot (thrombosis) at the injury site. This makes the artery even narrower and further reduces blood flow.
Thrombosis can cause angina, which is felt as pain in the chest, or result in stroke or heart attack, depending on which artery is affected. Thrombosis can also arise in veins, such as deep vein thrombosis of the leg.
ApoA-IV blocks platelets
In order to form a clot, platelets have to stick to each other. This happens through a bridge made from a protein called fibrinogen, which connects to the platelets by binding to integrin αIIβ3 receptors on their surfaces.
Using human blood samples and mice, Ni and his colleagues found that ApoA-IV can reduce platelet aggregation in blood vessels by blocking their integrin αIIβ3 receptors and thereby stopping them binding to fibrinogen.
They also found that ApoA-IV can help prevent blockage in blood vessels by changing shape, which eases blood flow.
The findings also explain why having more ApoA-IV in the blood can slow down atherosclerosis, says Ni, “because this process is also related to platelet function.”
He and his team then went on to examine how ApoA-IV interacts with food. It is usual, after a meal, for platelet activity to increase. Also, when we eat foods rich in unsaturated fats, blood levels of ApoA-IV go up.
Link to unsaturated fats and good sleep
The researchers suggest that the rise in ApoA-IV blood levels following meals containing olive oil and other unsaturated fats reduces “platelet hyperactivity and bonding,” which, in turn, reduces inflammation and stroke and heart attack risk.
Further investigation found a link with sleep. It seems that ApoA-IV is busiest when we are asleep at night, and its lowest level of activity is in the morning.
“So, we are protected by this protein while we sleep,” states Ni, “and most likely to experience a cardiovascular event after waking up in the morning.”
The researchers say that their findings support the idea that eating foods high in unsaturated fats, together with “appropriate sleep patterns,” are the ideal conditions for helping ApoA-IV lower the risk of atherosclerosis, stroke, and heart attack.
The scientists’ next step will be to study ApoA-IV in more depth with a view to using it in therapies for cardiovascular disease and possibly other conditions caused by problems with blood platelets.
“This is the first study to link ApoA-IV with platelets and thrombosis.”
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