Protein TG2 Identified as Potential Target for Hypertension Treatment

Controlling high blood pressure remains a persistent challenge for nearly half of U.S. adults, prompting researchers at the University of Missouri to investigate a new potential treatment target. The team is examining whether a protein called TG2, present in blood vessels and certain immune cells, can help reduce inflammation linked to hypertension.

TG2’s Role in Immune Cells

While previous research connected TG2 to arterial stiffening through its activity in blood vessels, the protein also exists in immune cells that regulate inflammation. This dual presence raised questions about whether TG2 activity within these cells contributes to high blood pressure. To address this, Camila Manrique-Acevedo, a professor at the university’s School of Medicine and investigator at Roy Blunt NextGen Precision Health, collaborated with Guido Lastra, an associate professor whose laboratory studies TG2.

Lastra led the study, which received support from the U.S. Department of Veterans Affairs. The research focused on female mice, comparing those with normal TG2 levels in myeloid cells—immune cells including white blood cells involved in inflammation—against mice genetically modified to lack TG2 in those specific cells.

Effects of Removing TG2

Both groups of mice were administered angiotensin II, a hormone that helps regulate blood pressure. Mice with normal TG2 levels developed expected increases in blood pressure, inflammation, and arterial stiffness. In contrast, mice lacking TG2 in their myeloid cells showed smaller responses to the hormone. The removal of the protein lessened these effects rather than eliminating them entirely.

These findings suggest that targeting TG2 could help address the inflammation that contributes to hypertension, a condition that significantly increases the risk of heart attacks and strokes. Although many factors contribute to the disease, identifying specific biological processes may offer researchers more precise ways to intervene.

Implications for Human Treatment

“High blood pressure increases the risk of cardiovascular disease tremendously, and while there are effective medications out there, many people still struggle to control their hypertension,” said Manrique-Acevedo. She noted that better understanding the underlying mechanisms could eventually lead to more precise treatments with potentially fewer side effects.

Manrique-Acevedo, who treats patients at MU Health Care’s University Hospital and works as an endocrinologist at Harry S. Truman Memorial Veterans’ Hospital, emphasized that the current study focused exclusively on female mice. Future research will need to examine what happens when TG2 is removed from the same cells in males to clarify if the effects differ by sex.

“Tailoring treatments for those who can benefit the most is what precision medicine is all about,” she said. Whether blocking TG2 activity can safely and effectively treat high blood pressure in humans remains to be established.

Study Publication Details

The research was published in the American Journal of Physiology-Heart and Circulatory Physiology on 30 September 2026. The paper, titled “Myeloid transglutaminase 2 regulates Treg-Th17 balance in a female model of angiotensin II-induced hypertension and vascular stiffening,” lists Huina Niu, Emma Teixeira, Camila Manrique-Acevedo, and Guido Lastra as authors. The study’s DOI is 10.1152/ajpheart.00095.2026.