ELIMINATION of the FOXM1 gene could improve outcomes for pulmonary hypertension patients, according to the findings of a recent study by researchers at Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA. These findings show promise for a new treatment target in pulmonary hypertension, with a hope of improving prognosis for patients.
Patients with pulmonary hypertension experience damage to the right side of the heart as a result of the condition. Currently, only 50% of patients survive for 5 years after diagnosis and there are no drugs that specifically target vascular remodelling in this condition. FOXM1 is known to control cell growth and there have been studies investigating its role in cancer proliferation; therefore, the team focussed their efforts on this gene.
Using genetically modified mice, the researchers discovered that when FoxM1 was missing from smooth muscle cells, mice did not develop thicker artery walls or high blood pressure within the lungs, factors that are characteristic of pulmonary hypertension. They also found that in pulmonary hypertension, damaged endothelial cells in the lining of the inner artery wall release growth factors that activate FoxM1. This damage to the endothelial cells is thought to be the first event that triggers the development of pulmonary hypertension. When FoxM1 is activated, a series of signalling pathways are initiated, inducing increased production of smooth muscle cells in the middle of the artery wall, resulting in the characteristic thickening.
The researchers hold high hopes for these new findings and suggested that compounds against FoxM1 could be used to reverse vascular remodelling: “We will now focus on developing new drugs that will inhibit the FOXM1 gene and hopefully improve outcomes for patients with pulmonary hypertension”, commented lead author Dr Zhiyu Dai, Stanley Manne Children’s Research Institute. With a considerably poor survival rate currently attributed to this patient group, studies and findings such as these show real promise for the future of pulmonary hypertension patients.