Atherosclerosis: EPA and DHA protect endothelial cells from free radicals

EPA and DHA's ability to counteract atherosclerosis appears to be due, at least in part, to the protective action these fatty acids exert on the endothelial cells that line blood vessels and exert functions critical to vascular health. In fact, according to the results of a new study, omega-3s are reportedly able to help endothelial cells protect their DNA from oxidative damage exerted by free radicals, reducing that damage by nearly 50 percent.

The discovery, published in the journal PlosOne, was conducted in recent months by researchers at the University of Fukushima (Japan). 

Omega-3s counteract cardiovascular risk 

Since a famous epidemiological study on Greenland Eskimos conducted in the 1970s, which revealed the correlation between high consumption of fatty fish and low incidence of cardiovascular disease, numerous researches have revealed the wide range of beneficial properties of omega-3s. In fact, omega-3s can counteract increased blood pressure and hinder the formation and development of plaques responsible for atherosclerosis, which, by clogging the arteries, can cause heart attack and stroke. Therefore, consumption of EPA- and DHA-rich foods or supplements is recommended to reduce cardiovascular risk, treat hypertriglyceridemia, reduce inflammation, and to improve endothelial function. Endothelium is the tissue that lines the inner surface of blood vessels. 

It is not just a simple lining tissue but regulates numerous mechanisms: it plays a central role in blood pressure regulation, as well as in thermoregulation, coagulation, inflammation and edema, and control of blood-tissue exchanges. Malfunctioning of the endothelium, that is, endothelial dysfunction, is involved in the development of atherosclerosis, and is believed to be one of the earliest symptoms of disease progression. The mechanisms by which EPA and DHA modulate endothelial function have not yet been elucidated. Recent studies suggest a link between DNA damage and atherosclerosis. Some research has identified mutations in the genes of a DNA repair protein in patients with certain diseases and early onset of atherosclerosis, suggesting a strong link between DNA damage and atherosclerosis. 

Numerous agents can damage genetic material, but reactive oxygen species (ROS), so-called free radicals, are the most frequent cause. Therefore, reducing ROS-induced DNA damage may be crucial for the prevention of atherosclerosis and related cardiovascular diseases. 

EPA and DHA reduce DNA damage by 50%.

In the new study, scientists investigated the effects of omega-3s on chromosomal DNA integrity in human endothelial cells to identify their ability to counteract atherosclerotic plaque formation and the possible molecular pathways involved. The researchers then determined the effect of DHA and EPA on endothelial cell damage caused by hydrogen peroxide, finding that in cells previously treated with EPA and DHA, oxidative damage was reduced by nearly 50 percent, in particular the extent of DNA breaks was less. 

In addition, omega-3 treatment decreased the activation of a molecule involved in the DNA damage response. These results underscore that omega-3s can minimize DNA damage regardless of the response mechanism that is activated in cells. According to the researchers, based on these findings and evidence from recent years, omega-3s could prevent the progression of atherosclerotic plaques and promote plaque stability, in part by inhibiting DNA damage, resulting in reducing senescence, cell death and inflammation as well. According to Harry Rice, vice president of the Organization for EPA and DHA (Goed), the positive role of omega-3s on cardiovascular health is now well established but the mechanisms by which this occurs remain to be elucidated. Just as this research, although very interesting, does not yet provide conclusive evidence on the protective mechanisms exerted by omega-3s. 

Some details of the research

During the study, researchers exposed human aortic endothelium cells to a solution containing EPA or DHA, and then to hydrogen peroxide (hydrogen peroxide), a potent oxidant that induces breaks in DNA. Immunofluorescence staining showed that the formation of γ-H2AX, a molecule indicative of DNA damage, was significantly reduced in cells treated with EPA and DHA, by 47 percent and 48 percent, respectively . In addition, a key molecule in the DNA damage response activated by hydrogen peroxide, called ATM, was significantly reduced after treatment with EPA and DHA, by 31% and 33%, respectively. The synthesis levels of some antioxidant molecules were significantly increased, while the decrease in reactive oxygen species occurred. Another effect of EPA and DHA was the reduction, by 31% and 22%, in the activity of β-galactosidase, an enzyme associated with senescence and cellular aging. 

The action of omega-3s on the genome reduces the risk of atherosclerosis

According to the researchers who conducted the study, their findings confirm that EPA and DHA attenuate oxidative stress-induced DNA damage in vascular endothelial cells through upregulation of the antioxidant response. Although further studies are needed to confirm this hypothesis, omega-3 fatty acids could also prevent cardiovascular disease through their genome-protective properties. Source: Sakai et al, "Fish oil omega-3 polynsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells." PlosOne.