Molecule May Offer Novel Bio-Marker for Male Hypertension

A team of scientists says that high levels of the molecule HMGB1 may help explain why men are more likely to become hypertensive earlier and more severely than women.

A research group led by Jennifer Sullivan, PhD, pharmacologist and physiologist at the Medical College of Georgia at Georgia Regents University, says it has uncovered evidence that a greater release of HMGB1 occurs in male rats, which likely equates to a persistent hypertensive response. 
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The molecule—which fuels inflammation and higher blood pressure inside the cell nucleus—plays a role in stabilizing DNA, and becomes dangerous when escaping, according to Sullivan, who is the principal investigator on an American Heart Association (AHA) grant designed to help identify some of the gender differences in hypertension. While HMGB1 is not the initiator of hypertension, the molecule could be an early target for intervention, especially among patients who struggle to control their blood pressure even with the use of multiple medications, says Sullivan.

With the AHA grant, Sullivan and her colleagues intend to further test its hypothesis that HMGB1 in males is activating T cells along with adhesion molecules that enable immune cells to stick to the blood vessel lining. As a result, inflammation and vascular damage multiply, and blood vessels are rendered unable to properly dilate. While drugs currently used to treat hypertension directly target the immune response, there is already evidence that HMGB1 activates the immune response in stroke, acute renal failure, and injury, as well as pulmonary hypertension, says Sullivan.

While noting that hypertension is the most common independent risk factor for cardiovascular disease, understanding the cause of hypertension “remains elusive,” says Sullivan.

“Until we better understand the initiating factors that result in an elevation in blood pressure, including gender-related differences, it is unlikely that blood-pressure control rates will improve, and hypertension-related morbidity and mortality will remain high,” she says.

Sullivan and colleagues are finding, however, that HMGB1 and immune-cell activation may be critical factors in the early stages of hypertension, she says.

“While broad acting, non-specific immunosuppressants are not justified in uncomplicated hypertension, targeting specific components of the immune system—such as HMGB1—may hold the potential to be therapeutically developed for widespread use to improve blood-pressure control rates in hypertensive patients,” says Sullivan.

As HMGB1 can be measured in people, the molecule “may serve as a novel bio-marker for hypertension.”

—Mark McGraw