Endothelial Microparticles are Associated to Pathogenesis of Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms remain unclear but involve a concomitant accumulation of scar tissue together with myofibroblasts activation. Microparticles (MPs) have been investigated in several human lung diseases as possible pathogenic elements, prognosis markers and therapeutic targets. We postulated that levels and cellular origins of circulating MPs might serve as biomarkers in IPF patients and/or as active players of fibrogenesis. Flow cytometry analysis showed a higher level of Annexin-V positive endothelial and platelet MPs in 41 IPF patients compared to 22 healthy volunteers. Moreover, in IPF patients with a low diffusing capacity of the lung for carbon monoxide (DL<40%), endothelial MPs (EMPs) were found significantly higher compared to those with DL>40% (p = 0.02). We then used EMPs isolated from endothelial progenitor cells (ECFCs) extracted from IPF patients or controls to modulate normal human lung fibroblast (NHLF) properties. We showed that EMPs did not modify proliferation, collagen deposition and myofibroblast transdifferentiation. However, EMPs from IPF patients stimulated migration capacity of NHLF. We hypothesized that this effect could result from EMPs fibrinolytic properties and found indeed higher plasminogen activation potential in total circulating MPs and ECFCs derived MPs issued from IPF patients compared to those isolated from healthy controls MPs. Our study showed that IPF is associated with an increased level of EMPs in the most severe patients, highlighting an active process of endothelial activation in the latter. Endothelial microparticles might contribute to the lung fibroblast invasion mediated, at least in part, by a fibrinolytic activity.

Standardization of methods to quantify and culture endothelial colony‐forming cells derived from peripheral blood

“…Whether this holds true in other clinical situations, such as diabetes, remains to be determined . Often, particularly in vascular genetic disorders, the main changes are not in the levels of ECFCs but in some of their functional properties, including proliferation capacity, vesiculation, and the onset of senescence . Alternative measures for regenerative potential need to be explored, including expression of immaturity markers, the in vivo ability to form stable vessels, and long‐term proliferation.…”

SHIP‐1, a target of miR‐155, regulates endothelial cell responses in lung fibrosis

“…Several studies proposed the concept that lung endothelial cells and endothelial‐mesenchymal transition (EndoMT) play important roles in the pathogenesis of pulmonary fibrosis . However, the role of endothelial cells and the function and relationship of endothelial miR‐155 and SHIP‐1 in lung fibrosis remain unknown.…”

“…11,14 Several studies proposed the concept that lung endothelial cells and endothelial-mesenchymal transition (EndoMT) play important roles in the pathogenesis of pulmonary fibrosis. [15][16][17][18] However, the role of endothelial cells and the function and relationship of endothelial miR-155 and SHIP-1 in lung fibrosis remain unknown. We hypothesized that endothelial miR-155 mediates fibrotic responses in the lung through EndoMT; Endothelial SHIP-1, a target of miR-155, is essential in controlling fibrotic responses in the lung.…”

Treprostinil treatment decreases circulating platelet microvesicles and their procoagulant activity in pediatric pulmonary hypertension

“…Circulating Microvesicles (MVs) are extracellular vesicles with a diameter from 100 to 1000 nm, released by shedding from the surface of hematopoietic and endothelial cells . These MVs have the ability to interact with thrombotic process because of their procoagulant and also fibrinolytic properties .…”

“…4 Circulating Microvesicles (MVs) are extracellular vesicles with a diameter from 100 to 1000 nm, released by shedding from the surface of hematopoietic and endothelial cells. [5][6][7] These MVs have the ability to interact with thrombotic process because of their procoagulant and also fibrinolytic properties. 6 Moreover, besides their role in thrombosis, microvesicles can be considerate as bioactive effectors that carry other molecules derived from the parental cells, including proteins, DNA, RNA, and microRNAs.…”