University of Missouri identifies TG2 protein as hypertension target

• Researchers at the University of Missouri identified that the protein TG2 in myeloid immune cells contributes to inflammation and arterial stiffness in high blood pressure.
• The findings point toward potential new precision medicine targets for patients who struggle to control hypertension with standard medications.

High blood pressure remains a persistent clinical challenge for nearly half of all adults in the United States. While standard antihypertensive medications lower systemic pressure, cardiovascular risk persists for many patients because current therapies do not directly address the underlying immune-driven pathogenesis and vascular remodeling. To investigate alternative biological pathways, investigators examined the role of TG2, a protein previously implicated in arterial stiffening.

Led by Guido Lastra, an associate professor in the University of Missouri School of Medicine, the research team sought to determine whether TG2 activity inside immune cells actively promotes hypertension. The study evaluated myeloid cells, a group containing white blood cells involved in inflammation. Investigators compared mice with normal TG2 levels against a cohort in which the protein was genetically removed specifically from these myeloid cells. Both experimental groups received infusions of angiotensin II, a potent peptide hormone that regulates blood pressure and induces vascular pathology.

Mice possessing normal TG2 levels developed expected pathological surges in blood pressure, heightened inflammatory markers, and progressive arterial stiffness. Conversely, subjects lacking TG2 in their myeloid cells demonstrated attenuated responses. Removing the protein lessened the pathophysiological effects rather than entirely abolishing them, suggesting that TG2 acts as a key driver within a multi-factorial disease network.

Camila Manrique-Acevedo, a professor at the University of Missouri School of Medicine, investigator at Roy Blunt NextGen Precision Health, and treating physician at MU Health Care’s University Hospital and Harry S. Truman Memorial Veterans’ Hospital, noted the clinical implications of the work. “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,” Manrique-Acevedo stated. She added that identifying underlying mechanisms could eventually yield more precise treatments with fewer adverse side effects.

The study received financial support from the U.S. Department of Veterans Affairs via resources and facilities at the Harry S. Truman Memorial Veterans’ Hospital in Columbia, Missouri, alongside Grant VA 5I01BX001981, the Department of Medicine at the University of Missouri, and the Thomas W. Burns Research Endowment. Authors Huina Niu, Emma Teixeira, Camila Manrique-Acevedo, and Guido Lastra contributed to the peer-reviewed paper.

Translating these laboratory insights into human therapeutics requires additional clinical investigation. Because the current study evaluated a female model, future research must determine whether male subjects exhibit identical cellular responses when TG2 is depleted. Clarifying sex-specific differences remains a cornerstone of modern translational medicine as researchers attempt to match targeted biological interventions with the patient populations most likely to benefit.

*Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.*