Radiation and Cardiovascular Health

• août 01 2022, par SANUSq Research team

Radiation and Cardiovascular Health. Researchers have been trying to pin down the risks of low doses of ionizing radiations for ages. And in this regard non-cancer diseases are not considered real health risks in the traditional sense.

However, recent epidemiological studies suggest that populations exposed to ionizing radiation are at an increased risk of heart disease. [1] In fact, some studies have linked doses around 0.5 Gy to this amplified risk with a long lag time, up to decades. [2] [3]

Now, a new research published in the International Journal of Radiation Biology found that low exposure to doses of around 0.5 Gy significantly increases the risk of cardiovascular damage, up to decades after exposure. [4] This apparently tiny dose is what you would receive after repeated CT scans.

Damage to endothelial cells is the key

Previous studies have spotlighted the role of ionizing radiations in developing cardiac injury via damaging endothelium [5].

What is endothelium? It is a wafer-thin layer of cells that lines the inner surface of all the blood vessels and also several organs such as heart and lymphatic vessels. Comprising of trillions of cells, endothelium is one of the most amazing parts of your body with some extraordinary functions.

Most importantly, it provides a physical barrier between the tissues and the flowing blood. And it also produces chemicals, such as nitric oxide (NO) that control the dilation and contraction of your blood vessels. A healthy endothelium helps in healthy blood flow, regulates wound healing in tissues, actively supresses inflammation in the arteries and prevents formation of blood clots in blood vessels. Overall, the endothelium works hard to create a favourable environment for your heart and vascular health.

Endothelium dysfunction is already known to play a central role in the development of atherosclerosis and coronary heart disease. [6] [7] High blood pressure, cigarette smoke, high blood sugar, chronic stress, sedentary lifestyle, poor diet and ageing are all usual suspects in causing damage to the endothelium.

Going by this new research, you can now add ‘long term exposure to low dose ionizing radiations’ to this list.

Study highlights

The team studied how the endothelial cells of the human coronary artery respond to a relatively low radiation dose of 0.5 Gy. The researchers found long-term, irreversible changes in the cells, that could negatively impact their functions.
Let’s take a closer look at molecular and cellular mechanisms involved in setting off this damage.

1. Reduced levels of NO

The study found that low dose radiation reduces NO levels in the endothelial cells by influencing certain signalling pathways. More specifically, radiation activates RHoA signalling, which inhibits an enzyme responsible for synthesising NO.

Nitric Oxide is one of the most important molecules when it comes to heart health. It helps blood vessels to dilate and prevents platelets from sticking to the vessel walls, thus ensuring smooth flow of blood throughout the body. NO is also involved in regulating many other critical processes like oxidation and inflammation. If not strictly controlled, these processes can damage your heart’s vascular system.

2. Increased amounts of reactive oxygen species

Low NO levels also lead to increased production of reactive oxygen species (ROS), which harms vascular functions through several mechanisms. On one hand, this causes oxidation of lipids, DNA and proteins. (In fact, such chronic oxidative stress and resulting inflammation form an important part of how radiations cause damage.) On the other hand, increased ROS formation in endothelial cells further decrease NO levels, creating a vicious cycle.

3. Reduced capacity to eliminate oxidized proteins

The study found a significant increase in protein carbonylation, a marker of irreversible oxidative damage. Such modification in proteins (triggered by ROS induced oxidative damage) cause loss of protein function. This creates a need to degrade and eliminate oxidized, damaged proteins.

Now, endothelial cells maintain a highly efficient ‘Ubiquitin-Proteasome’ system, that helps to degrade oxidized protein and maintain protein quality control. Interestingly, the discovery of the ubiquitin-proteasome system (UPS) as the central system involved in the degradation of proteins in the living cells, received the Nobel Prize in Chemistry in 2004.

The study found that irradiation disrupts this Ubiquitin-Proteasome system. That’s why exposed cardiac endothelial cells in the study lost their efficiency in degrading damaged proteins – leading to accumulation of oxidized proteins and early premature aging of the cells.

According to the researchers all these molecular changes explain the increased risk of cardiovascular disease after low-dose radiation exposure, concluding that “even a moderate radiation dose of 0.5 Gy has a significant adverse impact on the endothelial proteome. Molecular alterations seen here support the data from population studies suggesting an increased risk for cardiovascular disease after exposure to 0.5 Gy.”

References:

1. Tapio S. 2016. Pathology and biology of radiation-induced cardiac disease. J Radiat Res. 57:439–448.
2. Azizova et al. Cardiovascular diseases in the cohort of workers first employed at Mayak PA in 1948–1958. Radiat Res. 2010.
3. Azizova et al. Ischaemic heart disease incidence and mortality in an extended cohort of Mayak workers first employed in 1948–1982. Br J Radiol. 2015
4. Azimzadeh et al. Proteome analysis of irradiated endothelial cells reveals persistent alteration in protein degradation and the RhoGDI and NO signalling pathways. Internation Journal of Radiation Biology. 2017
5. Slezak et al. Mechanisms of cardiac radiation injury and potential preventive approaches. Can J Physiol Pharmacol. 2015
6. Hadi HA, Carr CS, Al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005;1:183–98.
7. Widmer et al. Endothelial dysfunction and cardiovascular disease. Glob Cardiol Sci Pract. 2014

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