A human pulmonary artery showing a thickened vell wall (fibroblast cells in yellow), with diseased smooth muscle cells (cyan) occupying its opening. Image credit: Slaven Crnkovic and Julia Kohlbacher (CC BY 4.0).
Idiopathic pulmonary hypertension (IPAH for short) is a chronic disease that can lead to severe breathing difficulties and a higher risk of heart damage or other life-threatening complications. While drugs exist to help manage symptoms, none are currently curative.
IPAH mainly affects the pulmonary arteries, which are tasked with carrying the blood from the heart to the lungs to collect oxygen. The disease causes the walls of these vessels to thicken abnormally, obstructing blood flow and requiring the heart to work harder.
The outer layers of pulmonary arteries are formed of both fibroblast and smooth muscle cells: the fibroblasts produce proteins that support the structure of the vessel, while the smooth muscle helps control blood flow by contracting and relaxing. Both types of cells are involved in vessel wall thickening in IPAH, but what causes them to switch from a healthy to a diseased state remains unclear.
To examine this question, Crnkovic et al. compared the gene activity, protein production and behaviour of smooth muscle cells and fibroblasts obtained from the pulmonary arteries of healthy donors and IPAH patients. The experiments revealed that both types of cells showed similar impairments to their mitochondria, the cellular structures that help provide energy. However, differences also emerged. Diseased smooth muscle tissue produced the proteins that these cells use to contract and relax, ultimately impairing their ability to regulate blood flow to the lungs. Meanwhile, IPAH fibroblasts multiplied abnormally fast, potentially contributing to vessel thickening.
Growing smooth muscle and fibroblast cells together in the laboratory allowed Crnkovic et al. to examine how interactions between these cells could help drive the disease. This showed that the fibroblasts released signals which triggered IPAH-characteristic changes in normally healthy smooth muscle cells. As such, the ability of fibroblasts to ‘talk’ to smooth muscle cells could be important in the progression of the condition.
Crnkovic et al. hope that these findings will help develop better treatments to stop or reverse the progression of IPAH. However, further research is needed to confirm which biological processes should be targeted, and to ensure that reversing the abnormal changes in lung blood vessels is both safe and effective.
