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A study of over 1,000 patients with atherosclerosis reveals fat tissue secretes factors that can trigger or worsen blood vessel conditions linked to cardiometabolic disorders.

By clarifying the poorly-understood link between obesity and blood vessel conditions, the findings could help scientists create new therapies for vascular and metabolic diseases like coronary artery disease. The study is published in Science Translational Medicine

Obesity changes how fat tissue secretes signaling molecules, which in turn can influence the structure and function of blood vessels in the body.

Studies have implicated both the Wnt signaling pathway and oxidative stress from enzymes as contributors to vascular disease, but the mechanisms by which obesity affects these pathways remain a mystery. Seeking insight, Ioannis Akoumianakis (a DPhil student from the Antoniades group), together with researchers from OCDEM, Bristol Medical School and Athens University medical School, analyzed a group of 1,004 patients with atherosclerosis.

The researchers discovered that obese individuals showed much higher levels of a protein named WNT5A in plasma, as well as elevated expression of WNT5A receptors in the walls of arteries.

In a separate experiment, the authors saw that higher levels of WNT5A in plasma correlated with the development of calcified plaques – a key marker of vessel disease – in 68 patients with coronary artery disease.

Further studies showed obesity boosted the secretion of WNT5A from fat tissue surrounding blood vessels, which in turn increased oxidative stress and the migration of smooth muscle cells through the enzymes USP17 and RAC1.

The authors suggest that WNT5A and the enzymes it affects could be targeted in obese patients, although further work in animal models is necessary.

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