STAT5a/b Gene May Be Responsible for Gender Differences in Pulmonary Hypertension

A research group from New York Medical College has found a gene that may control pulmonary hypertension severity, as well as the less severe form that occurs in women versus men. The article appeared November 21, 2014, in the journal Molecular Medicine. entitled, “Deletion of STAT5a/b in vascular smooth muscle abrogates the male bias in hypoxic pulmonary hypertension in mice: implications in the human disease.”

Pulmonary hypertension (PH)  is high blood pressure of the lung arteries. More women than men have PH, but women with PH do not get as extreme a form as men and therefore tend to live longer.

PH is associated with other conditions, such as lung disease and heart disease. Genetics in part determine whether someone develops PH. Although PH incidence increases with age, people of any age may develop PH. The condition can result in heart failure and possible death, so understanding underlying causes and possible treatments is important.

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The STAT5 a/b gene has been shown to be responsible for gender-specific differences in other diseases. In the present study, the researchers studied mice that had been genetically modified to lack the STAT5 a/b gene in their smooth muscle cells. These cells make up the walls of blood vessels.

When male mice were subjected to a lack of oxygen (hypoxia) — which is a way of inducing pulmonary hypertension in the lungs — their blood vessels responded with changes that indicated hypertension. Female mice exposed to hypoxia only had a mild version of this hypertensive change.

When the female mice lacked the STAT5a/b gene and were exposed to hypoxia, they developed a severe form of pulmonary hypertension.

The scientists also looked at human lung tissue, and saw that where the lung arteries were damaged, there was also less STAT5 (the protein that STATa/b codes for).

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According to the authors of this study, “Taken together, these data provide the first definitive evidence for a contribution of STAT5a/b to the sex-bias in PH in the hypoxic mouse, and implicate reduced STAT5 in the pathogenesis of the human disease.”

The STAT a/b gene may control the severity of pulmonary hypertension and could be controlled by estrogen levels. This could explain why women do not get as severe pulmonary hypertension as men.

The study also indicates that STAT5 could be reduced in more severe cases of human PH. Targeting STAT5 might provide a method of treating PH.