Extracellular Vesicles as Biomarkers for Acute Respiratory Distress Syndrome

Kevin Fan

School Name

Academic Magnet High School

Grade Level

10th Grade

Presentation Topic

Physiology and Health

Presentation Type

Mentored

Abstract

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Acute respiratory distress syndrome (ARDS) is a secondary disease that may follow sepsis and is characterized by inflammation, increased vascular ermeability, and endothelial cell dysfunction. Currently, there are no approved pharmacological treatments. Extracellular vesicles (EVs) are membranous microvesicles secreted from the endosomal compartment or plasma membrane of cells. Recent evidence suggests that circulating EVs from septic patients are associated with inflammation and vascular permeability, so we investigated circulating EVs as potential biomarkers for sepsis-induced ARDS. To do this, we collected plasma samples from 85 ICU-administered septic patients, 21 of whom developed ARDS, as well as healthy controls. EVs were extracted from these samples and subsequently added to HMVECs. Transendothelial electrical resistance (TEER) assays were performed on the HMVECs, and the resulting data was used as an indication of vascular permeability. We found that EVs from ARDS patients (n=21) have a higher chance (81% vs 37.5%) to induce TEER compared to non-ARDS patients (n=64). These findings may eventually lead to a screening strategy to determine a patient's risk of ARDS development based on their EVs. We also wanted to explore potential explanations for this phenomenon. Previous studies suggest that EVs containing caspase-1 induce endothelial cell injury, so we determined caspase-1 activity in the EVs and discovered that EVs from septic patients contain significantly higher caspase-1 activity than healthy controls, and EVs from ARDS patients have higher caspase-1 activity than EVs from septic patients without ARDS.

Location

Furman Hall 201

Start Date

3-28-2020 10:14 AM

Presentation Format

Oral and Written

Group Project

No

COinS
 
Mar 28th, 10:14 AM

Extracellular Vesicles as Biomarkers for Acute Respiratory Distress Syndrome

Furman Hall 201

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Acute respiratory distress syndrome (ARDS) is a secondary disease that may follow sepsis and is characterized by inflammation, increased vascular ermeability, and endothelial cell dysfunction. Currently, there are no approved pharmacological treatments. Extracellular vesicles (EVs) are membranous microvesicles secreted from the endosomal compartment or plasma membrane of cells. Recent evidence suggests that circulating EVs from septic patients are associated with inflammation and vascular permeability, so we investigated circulating EVs as potential biomarkers for sepsis-induced ARDS. To do this, we collected plasma samples from 85 ICU-administered septic patients, 21 of whom developed ARDS, as well as healthy controls. EVs were extracted from these samples and subsequently added to HMVECs. Transendothelial electrical resistance (TEER) assays were performed on the HMVECs, and the resulting data was used as an indication of vascular permeability. We found that EVs from ARDS patients (n=21) have a higher chance (81% vs 37.5%) to induce TEER compared to non-ARDS patients (n=64). These findings may eventually lead to a screening strategy to determine a patient's risk of ARDS development based on their EVs. We also wanted to explore potential explanations for this phenomenon. Previous studies suggest that EVs containing caspase-1 induce endothelial cell injury, so we determined caspase-1 activity in the EVs and discovered that EVs from septic patients contain significantly higher caspase-1 activity than healthy controls, and EVs from ARDS patients have higher caspase-1 activity than EVs from septic patients without ARDS.