New Protein Target Discovered for High Blood Pressure and Inflammation

The Role of TG2 in Myeloid Cells and Vascular Stiffening

High blood pressure affects nearly half of U.S. adults, creating a persistent clinical challenge for long-term management and cardiovascular disease prevention. While TG2 was previously linked to arterial stiffening through research on blood vessels, researchers sought to determine whether its presence in immune cells also contributes to hypertension-related pathology. Led by associate professor Guido Lastra, the research team examined myeloid cells—a category of immune cells that includes white blood cells involved in inflammation—to observe how removing TG2 alters vascular and immune reactions.

In the study utilizing a female murine model, investigators administered angiotensin II, a hormone that regulates blood pressure and triggers arterial stiffening and inflammation. Mice with normal TG2 levels developed the expected increases in blood pressure, vascular stiffness, and inflammatory markers. In contrast, mice engineered to lack TG2 specifically in their myeloid cells showed blunted responses, experiencing smaller increases in pressure and arterial changes.

Investigating Precise Treatments for Resistant Hypertension

Camila Manrique-Acevedo, a professor at the University of Missouri School of Medicine, investigator at Roy Blunt NextGen Precision Health, and clinician at MU Health Care’s University Hospital and the Harry S. Truman Memorial Veterans’ Hospital, noted that understanding these mechanisms could eventually yield more targeted interventions. “If we can better understand the underlying mechanisms contributing to hypertension in the first place, perhaps that can one day lead to more precise treatments with potentially fewer side effects,” Manrique-Acevedo stated.

While the findings establish that myeloid TG2 activity modulates inflammatory and vascular responses, researchers emphasize that translating these results into human therapies requires further investigation. Because the current experiment focused exclusively on female subjects, upcoming studies will evaluate whether removing TG2 in male subjects yields comparable or distinct physiological effects. The research was supported by the U.S. Department of Veterans Affairs, the Department of Medicine at the University of Missouri, and the Thomas W. Burns Research Endowment.