Reinforcing the Endothelial Surface Layer to Prevent Lung Injury
Abstract
For over 150 years, military doctors have faced a challenging problem. Young, healthy Soldiers who had survived a battlefield injury would suddenly develop severe difficulty breathing, as their lungs unexpectedly filled with fluid. Today, this disease is known as "Acute Lung Injury" (or the "Acute Respiratory Distress Syndrome") and is a major problem in both civilian and military intensive care units. Despite being studied for decades, no effective treatment prevents the onset of Acute Lung Injury after an illness such as severe infection or trauma. The failure to find an effective prevention against Acute Lung Injury suggests that we need new ideas in our understanding of this common yet severe disease. Recent discoveries have identified the importance of a structure called the "Endothelial Surface Layer" to the onset of Acute Lung Injury. The Endothelial Surface Layer lines the inside of all blood vessels and is made of a sugar called "Heparan Sulfate." The Endothelial Surface Layer is particularly important in the lung -- without a normal Endothelial Surface Layer, the lungs fill with fluid and cannot work properly. We now know that illnesses such as infection or trauma can damage the lung Endothelial Surface Layer, leading to Acute Lung Injury. Thus, if we can find out how to protect the Endothelial Surface Layer in patients suffering from trauma or infection, we can possibly prevent Acute Lung Injury from ever occurring -- saving both lives and medical resources. Surprisingly, the lung has already figured out a way to protect its Endothelial Surface Layer. In animals who survived severe infection ("sepsis"), the lung constructs a reinforced Endothelial Surface Layer using modified Heparan Sulfate that is resistant to degradation. We propose to study this natural form of lung protection; by understanding how the lung protects itself, we can develop medications that accelerate or activate processes of Endothelial Surface Layer reinforcement, thereby preventing Acute Lung Injury in military personnel and civilians alike.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610183
Entities
People
- Eric F Schmidt
Organizations
- United States Army
- University of Colorado Denver