Can Endothelial Cells Lining Veins In Lungs Help Repair Injured Blood Vessels?

Researchers discovered that endothelial cells lining veins in the lungs can help fix blood vessels after injury.

The Findings

Researchers studying the role of pulmonary venous endothelial cells (VECs) in endothelial regeneration after lung injury have found that VECs can help fix damaged blood vessels in the lungs.

VECs line the inside of blood vessels in the lungs, playing an essential role in blood flow and angiogenesis, the creation of new blood vessels. The team discovered that following influenza, COVID, and hyperoxia injury, VECs proliferate into the adjacent capillary bed — a network of blood vessels facilitating gas exchange — and contribute to its repair and regeneration, which is essential for pulmonary function.

Study results also showed that VECs differentiate into capillary cells, and that this remodeling is a response to lung injury, not one that occurs during normal lung development after birth.

Why It Matters

Pulmonary veins play a significant role in lung function and in maintaining sufficient oxygen in tissue throughout the body. When a person sustains lung injury from an illness such as COVID or influenza, repair of blood vessels and the creation of new ones is vital to meet oxygen demands. Research in these areas is under-investigated despite this critical need.

VECs may provide crucial targets for therapies to enhance endothelial repair and improve patient survival in not only severe viral pneumonia and acute respiratory distress syndrome, but also neonatal lung disease related to developmental lung defects and prematurity.

Who Conducted the Study

Researchers from CHOP, the University of Pennsylvania's School of Veterinary Medicine, and the Perelman School of Medicine, including members of the Penn-CHOP Lung Biology Institute, Penn and CHOP Cardiovascular Institutes, and Vanderbilt University Medical Center, conducted the study. David Frank, MD, PhD, an attending physician in the Division of Cardiology at CHOP, was co-senior and co-corresponding author, along with Andrew Vaughan, PhD, at Penn Vet.

How They Did It

Combing through single-cell RNA sequencing data of pulmonary endothelial cells at 0, 20, and 30 days after influenza injury, the researchers identified a new population of capillary endothelium transcriptionally related to the pulmonary vein endothelium.

In addition, they discovered that the gene Slc6a2 was a new marker of pulmonary VECs. Working with a murine model based on this gene and given tamoxifen at varying intervals, they observed that VECs proliferate into the adjacent capillary bed upon influenza injury and hyperoxia injury — damage to the lungs caused by exposure to high levels of oxygen.

Veins branch out into the capillary bed after lung injury from influenza.

Their imaging analysis demonstrated that VECs proliferate and differentiate into general capillary and aerocyte capillary endothelial cells after infection, which contributes to the repair of the capillary plexus and is vital for gas exchange.

Quick Thoughts

"The data generated brings a new regenerative mechanism for blood vessel repair in the lungs of children and adults and demonstrates that the pulmonary veins are not a passive conduit for blood to travel back to the heart," Dr. Frank said.

"It also opens the door for identifying mechanisms and treatments for capillary and pulmonary vein disease such as pulmonary vein stenosis and pulmonary veno-occlusive disease that carry high mortality rates," Dr. Frank added. "Pulmonary vein disease is becoming one of the most rapidly growing infant patient populations at CHOP and carries an unmet need for care and research for these diseases."

What's Next

The study team's demonstration that VECs are capable of differentiation into capillary populations presents a shift in understanding the repair processes of the gas-exchanging capillary bed and will allow future studies to target the venous endothelium to potentially promote recovery after lung injury.

Where the Study Was Published

The study appeared in Nature Cardiovascular Research.