27 September 2019

How fat damages blood vessels

The harm of obesity to the cardiovascular system may be directly related to one of the secrets of adipose tissue

Marina Astvatsaturyan, Echo of Moscow

Charalambos Antoniades, a cardiovascular researcher, and his colleagues at the University of Oxford in the UK found that the fatty tissue surrounding the arteries of patients with coronary heart disease secretes a large amount of a protein called WNT5A, which, in turn, harms blood vessels.

The results of the study are published in the journal Science Translational Medicine (Akoumianakis et al., Adipose tissue–derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases).

Despite the fact that the study of the mechanism of this effect is at the very beginning, the authors of the discovery believe that the WNT5A protein is a good target for the development of new therapies and prevention of coronary heart disease, writes WebMD. "If we create a drug that turns off the production of WNT5A by fat cells, or blocks the effects of protein in the vascular wall, we can 'neutralize' obesity, preventing heart attack and stroke," says Antoniades.

Many studies indicate an increased risk of coronary heart disease in obesity, and it is generally believed that this is due to "indirect" reasons: obesity contributes to diseases that lead to cardiovascular problems, among them type 2 diabetes, high blood pressure and sleep apnea.

In their study, Antoniades and colleagues analyzed blood samples and tissues surrounding arteries from almost a thousand patients who had undergone heart surgery. Among other things, they found that obese patients are distinguished by high levels of WNT5A protein in the blood, and especially large amounts of this protein are released from adipose tissue around blood vessels. In addition, patients with high levels of WNT5A form "plaques" on the walls of the arteries much faster in the years following the operation.


Obesity leads to increased production of Wnt5a in perivascular adipose tissue (PVAT) and visceral adipose tissue (such as breast adipose tissue, ThAT), which leads to increased bioavailability of Wnt5a compared to its Sfrp5 inhibitor.

Plaques are deposits of fat, calcium and other substances that clog the arteries and can cause a heart attack and stroke. By itself, the analysis of patient samples does not yet unambiguously indicate the WNT5A protein as the root cause of the development of coronary heart disease. But scientists have received more direct evidence in in vitro laboratory studies. The cells of the walls of blood vessels under the influence of protein released more harmful compounds and entered a state conducive to the formation of plaques.

According to WebMD experts, even if the WNT5A protein pathway is only one direction in which obesity directly harms blood vessels, the discovery of Oxford scientists is an important step in understanding the specific mechanisms of the harmful effects of obesity.

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