A British study shows that high levels of the enzyme CYP1B1 found in the lungs could play a role in the development of pulmonary arterial hypertension. CYP1B1 is responsible for breaking down estrogen into harmful smaller molecules.
The findings, published in the American Heart Association’s journal Circulation could lead to new treatments to tackle the disease, which often affects younger, pre-menopausal women.
The researchers showed that CYP1B1 levels were elevated in the lungs of mice with pulmonary arterial hypertension, and that lowering CYP1B1 levels reduced the severity of the disease. A ‘toxic’ by-product of estrogen—called 16α-hydroxyestrone—was found in elevated amounts in the urine of mice that did develop the condition.
The researchers also examined a small number of lung samples from human patients with pulmonary hypertension—all of whom had elevated levels of CYP1B1. According to the researchers, these findings mean that targeting the enzyme with a specific drug in the future might make a difference for patients.
“Pulmonary arterial hypertension is more common in women, which has led to the suggestion that the higher estrogen levels found in women might be linked to higher risk. Up until now, though, studies in animal models haven’t come up with a clear answer,” said Shannon Amoils, research advisor at the British Heart Foundation, which co-funded the research. “This interesting study in mice, which also looked at human samples, shows that abnormal estrogen breakdown in the lungs may be an important factor. But many questions about this condition are still unanswered, and the next stage is to move on to examine this association more closely in patients.”
Source: University of Glasgow