Bold reality: Obesity may raise blood pressure not just through systemic inflammation, but by inflammatory signals released directly inside blood vessels. This is the key finding from UVA researchers led by Swapnil Sonkusare, PhD, which uncovers a fresh angle on how obesity drives hypertension.
In a groundbreaking study, UVA Health scientists show that smooth muscle cells—the cells lining the small blood vessels—can emit inflammatory molecules that disrupt neighboring endothelial cells, which normally regulate blood flow. This disruption makes vessels less able to dilate and raises blood pressure. In short, the very wall of the vessel seems to generate inflammatory signals that push blood pressure higher in obesity.
This shifts the focus from immune cells alone to vascular cells as active sources of inflammation within the vessel wall, offering a new target for treating obesity-related hypertension.
As Sonkusare explains, a harmful interaction occurs: one cell type releases a molecule called TNF that damages nearby cells and elevates blood pressure. Importantly, reducing this inflammatory communication can lower blood pressure in obesity, at least in preclinical models.
The obesity-to-high-blood-pressure link is substantial: more than 40% of adults are obese, and obesity-related low-grade inflammation is known to interfere with blood pressure regulation. It is estimated that over 65% of primary hypertension cases relate to obesity. Prior work focused on immune cells for inflammatory signals, but this study suggests vascular cells themselves can generate such signals.
To test the idea, researchers fed lab mice a high-fat diet and then analyzed inflammatory molecules released by cells in small arteries, comparing them with arteries from mice on a normal diet. They found that obese mice’s smooth muscle cells produced TNF, which hampered calcium signaling in nearby endothelial cells, reducing the vessels’ ability to dilate and driving up blood pressure. Notably, this TNF signal appeared in small arteries that govern blood pressure, but not in large arteries like the aorta.
Clinical relevance emerged when the team observed higher TNF levels in small arteries from obese patients compared with non-obese individuals. In promising early steps, a TNF-blocking drug mitigated the inflammatory effect and lowered blood pressure in obese mice; initial human cell studies hint at similar potential, though further work is needed.
The team is now exploring why smooth muscle cells produce TNF in obesity and how this inflammatory dialogue can be interrupted to prevent or reduce hypertension.
Findings are published in Circulation Research (https://doi.org/10.1161/CIRCRESAHA.124.326069). The authors include Kuppusamy, Ottolini, Chen, Daneva, Li, Heng-Mae Cheung, Rios, Radi, Garcia, Nwafor, Park, Tumanov, and Sonkusare. Funding sources include the NIH, the Cancer Prevention and Research Institute of Texas, and several international institutions.
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