Circulating microvesicles as potential biomarkers and mediators of Acute Respiratory Distress Syndrome in Sepsis

Abstract

The acute respiratory distress syndrome (ARDS) is a clinical condition of sudden failure of the respiratory system that usually develops in critically ill patients in conditions induced by systemic inflammatory response were sepsis is the most common cause of ARDS. The circulating inflammatory mediators can lead to lung inflammation, and the use of mechanical ventilation is required in most cases. The factors and the early sequence of events in ARDS are unknown. Microvesicles (MVs) are small vesicles secreted from a wide variety of cells, which contains proteins, lipids and are involved in cellular communication. The biologically active molecules carried by MVs can influence gene expression modulating angiogenesis, cell proliferation, and regulating the immune system in target cells. Because of the characteristics of its source cell and changes in plasma concentrations in pathological conditions, the MVs have gained increasing attention in the search for new biomarkers. In a recent study conducted by our group in patients with sepsis, we screening 754 microRNAs and observed 65 differentially expressed in circulating microvesicles compared to the healthy subjects. In addition, 19 microRNAs was significantly correlated with patients who progressed to death. Since patients with sepsis may or may not develop ARDS, we intend to further study the previously identified microRNAs, investigating their expression levels between patients who developed ARDS, correlating with more detailed clinical data. We will use samples from the Biobank of the Intensive Care Unit of the Sirio-Libanes Hospital, were blood is collected within 24 hours of admission and 72 hours after the first collection. MVs will be isolated from plasma and 48 microRNAs will be measured by real time PCR. We will also investigate whether the isolated circulating MVs transport protein markers of tissue injury from the lung epithelium. We will investigate how these vesicles are modified by important clinical factors and whether they can serve as biomarkers of lung injury in sepsis. (AU)