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New approach to reducing damage after a heart attack

New approach to reducing damage after a heart attack

During the emergency procedure used to reopen the blocked artery causing a heart attack, smaller “micro” blood vessels can remain constricted causing significant damage. A new study led by Associate Professor Neil Herring and published in the European Heart Journal has established a key cause behind this constriction and identified a potential therapeutic target to block the mechanism behind it.

Cardiovascular disease is the main cause of death in the UK and throughout the Western World. One of the most common ways in which that manifests is through heart attacks, which occurs when one of the heart’s arteries is blocked. During a heart attack part of the heart starts to die, which causes pain in the chest and can be life-threatening.

Large heart attacks are treated with an emergency procedure to reopen the blocked artery using a balloon and metal tube called a stent. Whilst this procedure is often life saving, in around one third of cases smaller “micro” blood vessels beyond the stent remain constricted causing significant damage. The cause of these micro-vessels being very tightly constricted has so far been unclear.

A new study led by Professor Neil Herring has shed light on why this may happen. Innovative new research has uncovered evidence that the issue relates to the amount of stress the patient experiences during the heart attack. As part of the stress response, a neurotransmitter called Neuropeptide-Y (NPY) is released which causes micro-vessels in the heart to constrict. Furthermore, their data has demonstrated that patients with high NPY levels tend to go on to experience more heart damage.

To establish these results, the team studied patients who had experienced large heart attacks. They measured the levels of NPY both within the heart and peripheral blood. Alongside this, they took accurate and sophisticated measures of how constricted the small blood vessels were at the time. Through state of the art scans at 48 hours and 6 months after heart attack, researchers were able to see how much damage had been done to the heart. ‘We were able to correlate quite nicely the levels of NPY in the heart with how constricted the blood vessels were and even how much damage was done to the heart 6 months later,’ said Professor Herring.

The next step was to understand the mechanism behind how NPY causes this constriction. By studying isolated blood vessels in an animal model, researchers identified a key receptor that NPY binds to to cause the construction. They were then able to compare these results with samples of human hearts taken at the time of surgery, which clearly demonstrated that the receptor is also present in the human heart.

The crucial finding at this stage indicated that drugs that block the NPY receptor can reduce the damage of a heart attack in an experimental model. ‘That gives us real impetus to say if we can come up with a drug that we can use in humans that can block that receptor, then this may be a really good new treatment that we may be able to give to heart attack patients,’ said Professor Herring. Further studies are needed to establish whether NPY blocking drugs reduce the damage caused by a heart attack in patients and help improve survival.

The study is in collaboration with the Herring Group, the Oxford Acute Myocardial Infarction (OxAMI) Study led by Professor Keith Channon from the Oxford Heart Centre and the Radcliffe Department of Medicine, and Professor Kim Dora at the Department of Pharmacology. The research was supported by the British Heart Foundation and has been published in the European Heart Journal.

The full publication, ‘Neuropeptide-Y causes coronary microvascular constriction and is associated with reduced ejection fraction following ST-elevation myocardial infarction,’ can be read in the European Heart Journal.

Materials provided by University of Oxford

Heart attacks clotting

Scientists discover how human arteries are attacked by “bad cholesterol”

Researchers from the University of Texas Southwestern Medical Centre say that the formation of narrow blood vessels can lead to heart attack and strokes too. SR-B1 is a kind of protein which carries LDL particles over the endothelial cells which line the arteries. The study of how it carries the particles was published in the Nature journal.

In that study, it was also detected that a second protein known as dedicator of cytokinesis 4 or also called as DOCK4 are also associated with SR-B1 and also essential for the process. Dr. Philip Shaul, a senior author of the study said that the low-density lipoprotein which is commonly known as LDL cholesterol when enters into the artery wall leads to the growth of atherosclerosis or thickening of arteries. As a result of which, it turns into heart attacks and strokes. He also added that if treated in the future, to prevent the formation of these processes, it may help in reducing the occurrence of life-threatening state.

In the early stages of atherosclerosis what happens is that the LDL which enters in the artery wall attracts and is submerged by the vital immune system cells commonly known as macrophages which ingest or eats the LDL particles. These LDL laden macrophages become the foam cells which leads to swelling and the development of atherosclerotic plaques. These plaques narrow the arteries and become very unstable and the plaques which burst can trigger in the clotting of blood and can block the flow of blood towards the brain or heart. This can result in a stroke or heart attack.

In a recent study of mice with elevated cholesterol, the researchers said that the removal of SR-B1 from the cell resulted in the lessening of LDL entering the artery wall. This leads to the formation of lesser foam cells and smaller plaques. Dr. Shaul also mentioned that before working in this research the entry of LDL was unknown and thus the paper finding also solved the doubt of scientists LDL doesn’t enter through the damaged sites.

Scientists said that in their research they found out that atherosclerotic lesions are common due to the presence of more SR-B1 and DOCK4. To check if the same theory applies to human bodies the researchers viewed data on atherosclerotic and normal arteries from humans in three independent databases maintained by NIH. As a result, it was seen that SR-B1 and DOCK4 were huge in atherosclerotic arteries than normal ones.