A bold new insight links obesity to high blood pressure right inside the vessels themselves, reshaping how we understand this common health issue. Researchers at UVA, led by Swapnil Sonkusare, PhD, have uncovered a previously unknown mechanism by which obesity drives elevated blood pressure, occurring within the walls of blood vessels rather than solely through external factors.
In UVA Health’s cardiovascular research effort, Sonkusare and colleagues found that obesity triggers smooth muscle cells—the cells lining small arteries—to release inflammatory molecules. These signals mess with neighboring endothelial cells, which normally help regulate blood flow, causing a cascade that raises blood pressure.
This surprising finding shows that vascular cells can produce inflammatory molecules—an area once thought to be the exclusive domain of immune cells. By identifying this intra-vessel inflammatory communication, the study opens up a promising new target for treating obesity-related hypertension.
“We’ve identified a harmful interaction between neighboring cells in the vessel wall that raises blood pressure in obesity. In this interaction, one cell type emits an inflammatory signal called TNF, which damages the function of nearby cells and elevates blood pressure,” explained Sonkusare, who is part of UVA’s Robert M. Berne Cardiovascular Research Center. “Crucially, reducing this inflammatory dialogue can lower blood pressure in obesity.”
Obesity and Hypertension: A Growing Connection
More than 40% of adults are obese. This excess weight is known to sustain chronic, low-grade inflammation that can disrupt the body’s ability to manage blood pressure. It’s estimated that obesity underpins more than 65% of all cases of primary (essential) hypertension, where there isn’t a single identifiable cause.
Earlier research on obesity-related hypertension largely focused on immune cells because these cells can release inflammatory signals affecting both smooth muscle and endothelial cells. The UVA team, however, hypothesized that the blood vessels themselves might generate inflammatory molecules as well.
To test this idea, researchers fed lab mice a high-fat diet and analyzed the inflammatory signals released by individual cells within small arteries. They then compared these signals to those produced by the same cell types in mice on a normal diet.
Within blood vessel walls, smooth muscle cells and endothelial cells are the two primary cell types. The study found that smooth muscle cells from obese mice released TNF, an inflammatory molecule. TNF disrupted nearby endothelial cells’ ability to regulate calcium signaling, hindering vessel dilation and driving up blood pressure.
Importantly, TNF elevation was observed in small arteries that help control blood pressure, but not in large arteries like the aorta.
“Significantly, we also detected higher TNF levels in small arteries from obese patients compared with those from non-obese individuals,” noted Maniselvan Kuppusamy, PhD, a corresponding author.
Therapeutic Hope and Next Steps
Encouragingly, the researchers could counteract the inflammatory effect by using a drug that blocks TNF, which helped lower blood pressure in obese mice. Early experiments using human cell samples suggest this approach might work in people as well, though more work is needed before clinical use.
“We’re now investigating what triggers smooth muscle cells to produce TNF in obesity,” said Sonkusare. “By learning more about this inflammatory signaling, there may be new ways to interrupt it and reduce blood pressure.”
Publication and Support
The findings appear in Circulation Research (doi: 10.1161/CIRCRESAHA.124.326069). The research team includes Kuppusamy, Matteo Ottolini, Yen-Lin Chen, Zdravka Daneva, Jie Li, Caroline Heng-Mae Cheung, Natalia Rios, Rafael Radi, Gracie Garcia, Divine Nwafor, Min S. Park, Alexei V. Tumanov, and Sonkusare. The authors report no financial interests in the work.
Funding came from the National Institutes of Health (grants HL142808, HL167208, HL146914), the Cancer Prevention and Research Institute of Texas (grants RP210105, RP220470), and several programs from Universidad de la República and related institutions.
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