Not all blood vessel cells respond to injury in the same way

Millions of individuals across the globe face diseases that lead to lung scarring, a condition that frequently results in breathing troubles and diminished quality of life. Lung scarring, a primary characteristic of chronic lung ailments like pulmonary fibrosis, presents limited and ineffective treatment options. A recent collaborative research project conducted by Dr. Xaralabos Varelas and Dr. Giovanni Ligresti from the Boston University Chobanian & Avedisian School of Medicine has unveiled an unfamiliar group of cells in lung veins that become active following injury and contribute to scar tissue development, a process termed fibrosis.

This discovery of an unknown factor in lung fibrosis and a signaling pathway that can be targeted has opened up new prospects for devising treatments to prevent or decelerate the advancement of pulmonary fibrosis and other fibrotic lung conditions. The findings were published online in the journal Science Advances.

First author Kostas Kontodimas, a graduate student from the Department of Biochemistry and Cell Biology, highlighted that the study suggests the blood vessels in the lungs are not mere observers in fibrosis; instead, they might actively stimulate the disease via alterations in the specialized cells lining the lung vasculature. The scientists explored the onset of lung scarring and whether the cells lining blood vessels contribute to the formation of abnormal scar tissue.

Utilizing genetically modified experimental models and sophisticated laboratory techniques, the researchers selectively deactivated genes to maintain normal vascular cell functionality. Subsequently, they monitored the lung alterations over time. Additionally, they scrutinized thousands of individual lung cells to recognize which cell types were impacted and how they communicated during scar formation and progression.

Lastly, the team evaluated a drug that targets an overactive signaling pathway and discovered that this approach could prevent lung scarring while decreasing inflammation and vessel damage in preclinical models.

The implications of this research extend beyond lung scarring, as the scientists believe it challenges the conventional belief that the cells lining blood vessels primarily function as passive pathways for oxygen and nutrient delivery. The study's lead author, Varelas, a professor of biochemistry and cell biology, emphasized that the findings challenge the traditional view of blood vessel cells being passive conduits for oxygen and nutrients.

Instead, the researchers found that specialized blood vessel cells actively interact with their surroundings and can influence disease initiation and progression, suggesting that similar populations of blood vessel cells may be crucial in other conditions involving chronic inflammation or tissue scarring. This discovery opens up new avenues for research in a broad range of diseases.

While further research is required to ascertain the applicability of these findings to humans, the study offers vital insights into the development of pulmonary fibrosis and could potentially pave the way for more effective treatments for this debilitating disease.