Researchers at the University of Zurich have identified a potential breakthrough in treating cardiometabolic disease by targeting the thin layer of fat surrounding blood vessels. According to a study published in Cell Reports, using a BET inhibitor to suppress a specific enzyme in this fat layer reduces inflammation and restores the ability of arteries to dilate, potentially reversing early-stage cardiovascular damage.
Why does perivascular adipose tissue matter?
Most small arteries are wrapped in a layer of fat known as perivascular adipose tissue (PVAT). In a healthy body, this tissue helps vessels relax by sending beneficial signals. However, according to the University of Zurich research, this relationship turns destructive in patients with obesity and hypertension. The “vascular-fat interface” flips, causing the fat to release pro-inflammatory signals that damage the vessel lining, or endothelium. This damage prevents vessels from dilating, a process that acts as a precursor to heart attacks and heart failure.
How does the BET inhibitor RVX-208 restore vessel health?
The study found that the small molecule RVX-208 can “reprogram” the gene activity of diseased fat. Francesco Paneni, a cardiologist at the University of Zurich, notes that the team aimed to retune the fat’s entire gene program rather than targeting single downstream molecules. By inhibiting BET proteins—which amplify stress-related gene expression—the treatment reduced reactive oxygen species and restored nitric oxide production in vessel samples taken from 27 obese, hypertensive patients.
What is the role of the enzyme HK2?
Analysis of 84 cardiometabolic genes revealed that the enzyme hexokinase-2 (HK2) is a primary driver of this dysfunction. According to the Cell Reports study, diseased fat cells burn excessive glucose, which leads to mitochondrial dysfunction and inflammation. When researchers used a selective HK2 inhibitor on human vessel samples, they observed improved endothelial function, mimicking the benefits of broader BET inhibition. This suggests that the fat, rather than the vessel wall itself, is the primary source of the injury.
How does this compare to previous clinical trials?
Previous cardiovascular trials involving BET inhibitors often enrolled patients with end-stage disease, where cumulative damage may have obscured the treatment’s effectiveness. By identifying the specific role of PVAT and the HK2 enzyme, this research suggests that earlier intervention—targeting the fat-vessel interface before severe structural remodeling occurs—could provide more substantial patient outcomes. Future clinical strategies may need to prioritize the timing of these epigenetic therapies to catch the disease in its functional, rather than structural, phase.
Frequently Asked Questions
What is cardiometabolic disease?
Cardiometabolic disease is a condition characterized by a combination of obesity, high blood pressure, and metabolic dysfunction, serving as a leading cause of cardiovascular mortality, according to American Heart Association advisories.
Can this treatment be used now?
No. While these findings represent a significant scientific development, the research was conducted on human tissue biopsies and mouse models. Further clinical trials are required before this approach can be used as a standard treatment for patients.
What does the “vascular-fat interface” do?
It acts as a communication bridge between the fat surrounding a vessel and the vessel wall. In healthy individuals, it promotes relaxation, but in disease states, it promotes inflammation and constriction.
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