New Protein Target Could Tackle Hypertension
Scientists at the University of Missouri discovered that eliminating the TG2 protein from myeloid immune cells in female mice reduces angiotensin II‑induced blood pressure spikes, arterial stiffness, and inflammation. This finding suggests TG2 as a promising target for future hypertension therapies.
By Felo News Desk · Published
In a recent study published in the American Journal of Physiology‑Heart and Circulatory Physiology, researchers from the University of Missouri identified a protein that could become a new focus for treating high blood pressure. The protein, transglutaminase‑2 (TG2), is found in both blood vessels and a subset of immune cells called myeloid cells. By removing TG2 from these cells in female mice, the team observed a significant dampening of the rise in blood pressure, arterial stiffness, and inflammation normally triggered by the hormone angiotensin II.
Background: The Challenge of Hypertension
Hypertension, or high blood pressure, affects nearly half of U.S. adults and remains difficult to control for many patients despite the availability of effective medications. The condition is a major risk factor for heart attacks, strokes, and kidney disease. While lifestyle changes and drugs such as ACE inhibitors or beta‑blockers can lower blood pressure, a substantial portion of patients still struggle to maintain target levels. Scientists have long suspected that chronic inflammation plays a key role in the development and progression of hypertension, but pinpointing the exact molecular drivers has proven challenging.
Discovering TG2’s Role in Inflammation and Vascular Function
Transglutaminase‑2 has been previously linked to arterial stiffening—a hallmark of aging and hypertension—through studies on blood vessels. However, TG2 is also expressed in myeloid immune cells, which orchestrate inflammatory responses. The University of Missouri team, led by Professor Camila Manrique‑Acevedo and Associate Professor Guido Lastra, sought to determine whether TG2 activity within these immune cells contributes to the blood pressure‑raising effects of angiotensin II.
The researchers used a genetically engineered mouse model in which TG2 was selectively deleted from myeloid cells. Both TG2‑normal and TG2‑deficient mice were infused with angiotensin II, a hormone that naturally raises blood pressure and induces vascular inflammation. In the control group, the hormone produced the expected increase in systolic pressure, heightened arterial stiffness, and elevated inflammatory markers. In contrast, mice lacking TG2 in their myeloid cells exhibited markedly lower blood pressure elevations, reduced arterial stiffness, and a blunted inflammatory response.
Although the removal of TG2 did not eliminate the hypertension entirely, the attenuation of key pathological features indicates that TG2 in myeloid cells is a significant contributor to the disease process. The study’s findings suggest that targeting TG2 could help mitigate the inflammatory component of hypertension, potentially leading to more precise and side‑effect‑friendly therapies.
Implications for Future Treatments and Precision Medicine
Professor Manrique‑Acevedo, who also practices as an endocrinologist at Harry S. Truman Memorial Veterans’ Hospital, emphasized the importance of understanding underlying mechanisms to develop better treatments. “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,” she said.
The research team plans to investigate whether similar benefits occur in male mice, as the current study focused exclusively on females. Understanding sex differences will be crucial for tailoring therapies to the populations that stand to benefit most. Additionally, the study was supported by the U.S. Department of Veterans Affairs and the University of Missouri’s Department of Medicine, underscoring the potential relevance of these findings to veteran populations, who often face higher rates of hypertension.
Next Steps and Unresolved Questions
While the mouse model provides compelling evidence that TG2 in myeloid cells drives hypertension, translating these results into human therapies will require further work. Key questions include:
- Can pharmacological inhibition of TG2 safely reduce blood pressure in humans?
- What are the long‑term effects of TG2 suppression on immune function?
- Will TG2‑targeted therapies work across different age groups and comorbid conditions?
Clinical trials will be necessary to determine whether TG2 inhibitors can achieve the desired blood pressure reduction without compromising the immune system’s ability to fight infections. If successful, such treatments could complement existing antihypertensive drugs, offering a new avenue for patients who struggle with current medication regimens.
In summary, the discovery of TG2’s role in myeloid‑cell‑mediated inflammation opens a promising path toward more targeted hypertension therapies. By focusing on the protein’s activity within immune cells, researchers hope to develop drugs that address the inflammatory root of the disease, potentially improving outcomes for millions of people worldwide.
Key facts
- TG2 removal lowers blood pressure in mice
- TG2 links inflammation to arterial stiffness
- Targeting TG2 could lead to new hypertension drugs
- Further studies needed for human application
- Research supports precision medicine approach
Why it matters
Hypertension’s link to heart disease makes any new therapeutic target valuable; TG2’s role in inflammation offers a pathway to more precise, potentially side‑effect‑reduced treatments.
Frequently asked questions
What is TG2?
TG2 is an enzyme that cross‑links proteins and is involved in both vascular remodeling and immune cell regulation.
Why focus on myeloid cells?
Myeloid cells drive inflammatory responses that contribute to hypertension; TG2 in these cells appears to amplify that effect.
Will this replace current hypertension drugs?
It is unlikely to replace existing therapies immediately; it may complement them once safety and efficacy are proven.
Is the effect gender‑specific?
The study used female mice; future research will examine whether the same benefits occur in males.
What are the next research steps?
Developing TG2 inhibitors, testing safety in animal models, and eventually conducting human clinical trials.
Sources
- [1] scitechdaily.com — originally reported as “Scientists Discover a New Potential Treatment Target for High Blood Pressure”
