The discovery from UVA’s Swapnil Sonkusare, PhD, and colleagues breaks new ground in our understanding of how the body regulates blood pressure.
School of Medicine researchers have discovered an unknown way obesity causes high blood pressure – and it comes from within the blood vessels themselves.
UVA Health’s Swapnil Sonkusare, PhD, and colleagues found that obesity causes smooth muscle cells that line blood vessels to release inflammatory molecules. These molecules disrupt the proper workings of neighboring endothelial cells that control blood flow, driving up blood pressure.
The surprising discovery confirms that vascular cells within blood vessels can release inflammatory molecules – something long thought to be the domain of immune cells. The finding gives researchers an exciting new target for developing blood pressure treatments for people with obesity.
“We have discovered a harmful interaction between neighboring cells in the blood vessel wall that raises blood pressure in obesity. In this interaction, one cell type sends out an inflammatory signal called TNF, which damages the function of nearby cells and elevates blood pressure,” said Sonkusare, part of UVA’s Robert M. Berne Cardiovascular Research Center. “Our research also shows that reducing this inflammatory communication can lower blood pressure in obesity.”
Obesity and High Blood Pressure
More than 40% of adults are obese. Carrying this extra weight is known to cause chronic, low-grade inflammation that can interfere with the body’s ability to regulate blood pressure. It’s estimated that more than 65% of all cases of primary hypertension – high blood pressure without one obvious cause – are related to obesity.
Prior research into obesity-related hypertension has focused on immune cells because of their known ability to release inflammatory signaling molecules that affect endothelial and smooth muscle cells. But Sonkusare and his team suspected that inflammatory molecules might also be generated in the blood vessels themselves.
To determine if this was the case, the researchers fed lab mice a high-fat diet and examined the molecules released by individual cells within small blood vessels called arteries. They then compared those results with the molecules released by the same cells in lab mice fed a normal diet.
Smooth muscle cells and endothelial cells are the two main cell types in a blood vessel wall. The researchers found that smooth muscle cells from obese mice released an inflammatory molecule called TNF. This molecule interrupts the ability of neighboring endothelial cells to use calcium properly, robbing the vessels of their ability to dilate (expand) and driving up blood pressure.
Notably, the scientists report, TNF was released only in small arteries that regulate blood pressure and not in large ones such as the aorta in the heart.
“Importantly, we also observed increased TNF levels in small arteries from obese patients when compared to the arteries from non-obese individuals,” said researcher Maniselvan Kuppusamy, PhD.
Promisingly, the scientists were able to use a drug that blocks TNF to counter the effect of the inflammatory molecule and lower blood pressure in obese mice. Early tests in human cell samples suggest the approach may work in people as well, though additional research is needed.
“We are now studying what causes smooth muscle cells to produce TNF in obesity,” said Sonkusare, part of UVA’s Department of Molecular Physiology and Biological Physics. “Learning more about this inflammatory communication could help us find new ways to stop it and lower blood pressure.”
Findings Published
The findings have been detailed in the scientific journal Circulation Research. The research team consisted of 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 scientists have no financial interest in the work.
The research was supported by the National Institutes of Health (grants HL142808, HL167208 and HL146914); the Cancer Prevention and Research Institute of Texas (grants RP210105 and RP220470); and the Universidad de la República (Espacio Interdisciplinario 2020), Programa de Alimentos y Salud Humana (PAyS) IDB-R.O.U. (4950/OC-UR) and Agencia Nacional de Investigación e Innovación (Fondo María Viñas FMV_3_2022_1_172574).
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