Fat around arteries fuels heart disease from within
A thin layer of fat wraps around most small arteries. In healthy people, it helps vessels relax. In obesity and high blood pressure, it turns against them, driving inflammation and constriction.
Researchers at the University of Zurich studied small arteries taken from fat biopsies of 27 obese, hypertensive patients and compared them with arteries from lean, healthy controls. The patients’ vessels showed structural remodelling and a blunted ability to dilate in response to normal signals.
In healthy vessels, the inner lining (the endothelium) releases nitric oxide (NO), a gas that relaxes the surrounding muscle. In the patient arteries, NO production was reduced. At the same time, the vessels generated more reactive oxygen species and elevated levels of inflammatory molecules including IL-1β, IL-6 and TNF-α. Together, these changes keep the vessels chronically constricted.
Resetting an overactive gene programme
The team treated isolated vessels with a small molecule called RVX-208, a BET inhibitor. BET proteins recognise chemical tags on the spools around which DNA is wound and amplify the activity of stress- and disease-related genes. Blocking them calms this overactive programme.
After RVX-208 treatment, vessel relaxation improved, reactive oxygen species fell, NO production recovered, and inflammation was suppressed more effectively than with any single cytokine-blocking antibody. The researchers, publishing in Cell Reports, concluded that the approach retuned the fat’s entire gene activity programme rather than targeting one molecule at a time.
Why this matters for ageing
Endothelial dysfunction is an early marker of cardiovascular disease and worsens with age. The findings suggest that perivascular adipose tissue, the fat directly surrounding blood vessels, is an underappreciated therapeutic target. Whether BET inhibitors work clinically in patients with cardiometabolic disease still needs to be shown in larger trials. But the strategy is noteworthy: it targets the source of low-grade, chronic vascular inflammation rather than its downstream effects.