We often hear that inflammation in the body is dangerous, leading to chronic diseases such as coronary heart disease, diabetes, and cancer to name a few. But what exactly is inflammation, is it always a bad thing, and how does it affect our heart?
What is inflammation?
Inflammation is the body’s natural defence mechanism to protect itself against injury and infection (1). Inflammation is present when you sprain your ankle, after a strenuous workout or when you get sunburnt. This is acute inflammation – typically inflammation that is localised to a specific area, lasts a short period of time and resolves (1). When the inflammatory response goes on for too long and becomes more widespread in the body, this can lead to some of the more chronic diseases mentioned above (1).
How does our body react to inflammation?
Our body initially launches an attack with our immune cells; the white blood cells that are the first responders to sites of injury and infection to protect the area, creating the classic signs of redness and swelling (1). They are part of the innate immune system, the body’s surveillance system that flags dangers, pathogens (germs), and injuries. They release chemicals that kill bacteria or other foreign substances, and release protein messengers called cytokines to signal out to other cells to help regulate the inflammatory response (1). So, in these settings, inflammation is essential to promote healing and without it, the injuries could worsen. However, when these immune responders misfire, chronic inflammation can develop. This is a persistent, ongoing attack from the immune system and can result in the recruitment and accumulation of large numbers of immune cells to the site of injury, and an excessive inflammatory response (1).
Chronic inflammation has been linked to heart disease and stroke (2). Inside our arteries, inflammation can initiate atherosclerosis – the build-up of fatty deposits leading to the formation of cholesterol-rich plaques. Immune cells known as macrophages perceive these fatty deposits as foreign substances and attempt to ingest and remove the plaque (3). However, over time, the continuous build-up of plaque is too great for these macrophages to remove and they end up unable to remove the fatty deposits (3). They are known as ‘foam cells’ because they are laden with lipids, which gives them a foamy appearance. Eventually if the plaque becomes unstable and ruptures, it forms a clot that blocks blood flow to the heart or brain, triggering a heart attack or stroke (3). This is just the triggering event – inflammation can even have a role after a heart attack.
How can Inflammation affect the heart?
Exactly how inflammation affects the heart after a heart attack is a relatively new and ongoing area of scientific research. Atherosclerosis, is a disease of the blood vessels characterised by chronic inflammation, developing over decades whereas inflammation after a heart attack is more acute in comparison.
When a clot reaches the heart, there is a drop in the supply of oxygen to that part of the cardiac muscle, which results in the death of cardiac muscle cells. The signals released by dying cells can alert the immune system, and in the first 24 hours after a heart attack, a specific type of immune cells – neutrophils, arrive at the damaged area (4,5). Their job is to clear away any debris or junk left behind by dead cells. In doing so, they also send a chemical signal to tissue repairing immune cells (5). This helps to dispose of cells damaged by the heart attack, helping restore the heart to health.
The inflammatory and resolution phases after a heart attack – helping hearts scar
In the first 3-4 days after a heart attack, another type of immune cell (monocytes), travel to the heart and help in the removal of dead tissue (6,7). After the fourth day, there is a restoring ‘resolution’ phase where a scar develops. The monocytes can mature into macrophages which promote scar development that can lead to changes in the way the heart is structured, a process called cardiac remodelling. For example, when you cut yourself, to mend the damage, a fibrous tissue which is the scar replaces the normal tissue. If your heart is damaged, scarring is also a normal part of the healing process. But it’s far more important that the scar is balanced and stable to make sure the structure and shape of the heart stays as normal as possible. If there is too much inflammation, the healing process can become suboptimal, leading to a thin, stretched out scar and the development of heart failure. Heart failure is when the heart lacks the strength to pump blood around the body efficiently. It can be treated, but there is no cure.
Up and coming treatment options
In England there are over 157,000 hospital visits each year due to heart attacks (8). Survival rates have improved greatly over the last 50 years, but heart attacks cause permanent damage, there is a greater risk for a second attack and there is the potential for long-term problems including heart failure (8).
By identifying ways to prevent inflammation and encourage healing as quickly as possible, future treatments could vastly improve the outlook for patients living with heart failure.
The immune system is complex, and hugely important to help defend against disease. When thinking about treatments, there are a lot of considerations to be taken into account, as interfering with the immune system could have other unwanted effects in the defence against infection (9). Therefore, identifying ways to help the immune system to recover specifically from heart attacks without unwanted effects is crucial. Stopping the inflammatory response from going overboard would be a starting point, but it’s a fine line between too much and not enough.
Currently, cholesterol lowering drugs such as statins are given to heart attack patients to reduce their risk of another attack, and surgery to help restore blood to the heart (10). But we now know that not all heart attack sufferers have high cholesterol and sometimes lowering cholesterol alone is not enough. In the last two years, clinical trials targeting inflammation have shown promising results (9). The drug canakinumab which blocks a chemical signal that is part of the immune system has been shown to reduce repeat heart attacks by 15 %, and the need for bypass surgery in patients receiving this drug (11). If we combined these anti-inflammatory drugs with cholesterol lowering drugs, the risk of future heart attack could be lowered (11).
By understanding the mechanisms that control the action of immune cells in the wound healing process after a heart attack, we can use it to design therapies to optimise the immune systems response and ultimately save lives from heart disease.
(1) https://www.ncbi.nlm.nih.gov/books/NBK279298/ [accessed December 2018]
(2) Chamorro A, Hallenbeck J. The Harms and Benefits of Inflammatory and Immune Responses in Vascular Disease. Stroke. 2006 Feb; 37(2): 291–293.
(3) Ross, R. Atherosclerosis—An inflammatory disease. N. Engl. J. Med. 1999, 340, 115–126.
(4) Frangogiannis, N.G. The immune system and the remodelling infarcted heart: Cell biology insights and therapeutic opportunities. J. Cardiovasc. Pharmacol. 2014, 63, 185–195.
(5) Frangogiannis, N. G. Regulation of the inflammatory response in cardiac repair. Circ Res. 2012 110(1), pp. 159-73.
(6) Nahrendorf M, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007;204:3037–3047.
(7) Nahrendorf M, Swirski FK. Innate immune cells in ischaemic heart disease: does myocardial infarction beget myocardial infarction. Eur Heart J. 2016 Mar 14;37(11):868-72
(8) https://www.bhf.org.uk/what-we-do/our-research/heart-statistics [accessed December 2018]
(9) Jones DP, Patel J. Therapeutic Approaches Targeting Inflammation in Cardiovascular Disorders. Biology. 2018 Nov 16;7(4).
(10) https://www.bhf.org.uk/informationsupport/treatments/statins [accessed December 2018]