Researchers at the University of Zurich, University Hospital Zurich, and University of Pisa found that targeting epigenetic “readers” in perivascular fat — the fat layer surrounding blood vessels — can reduce inflammation and improve vessel health in both mice and human tissue. This approach may help prevent vascular damage in people with obesity and type 2 diabetes.
Why perivascular fat matters
Perivascular fat actively communicates with vessel walls to control relaxation and inflammation. In obesity and metabolic disease, this fat becomes inflamed, stores lipids abnormally, and releases molecules that stiffen vessels and impair function, contributing to early vascular disease, heart attacks, and strokes.
What the study did
Instead of targeting single downstream molecules, the team used BET protein inhibitors — epigenetic drugs that modulate how genes are “read” — to retune the entire gene activity program in perivascular fat cells.
Results
- In lab tests on mice and human tissue, the drugs shifted fat cells away from an inflammatory profile.
- Blood vessels surrounded by reprogrammed fat relaxed more easily and showed fewer signs of damage.
- A key driver identified was the enzyme hexokinase 2, which regulates sugar metabolism. Overactive hexokinase 2 makes fat cells store more fat and release inflammatory signals that harm vessels. Lowering its activity, either via epigenetic modulation or direct inhibition, blunted inflammation and restored normal vessel function in samples.
Potential impact
Led by UZH cardiologist Francesco Paneni, the study suggests epigenetic therapies could complement current treatments for blood pressure, cholesterol, and blood sugar. Rather than only managing downstream risk factors after damage starts, this approach aims to reprogram the tissue processes that cause vascular damage, potentially reducing progression to heart attack or stroke in obesity and metabolic disease.