Cellular microparticles in the pathogenesis of pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is a fatal disease with no treatment options, characterised by elevated pulmonary vascular resistanzce and secondary right ventricular failure. The aetiology of pulmonary arterial hypertension is multiple and its pathogenesis is complex. Although the exact role of cellular microparticles remains partially understood, there is increasing evidence to suggest an active role for microparticles in PH pathophysiology. Patients with PH exhibited higher circulating levels of microparticles compared to control subjects and in vitro or in vivo generated microparticles can induce endothelial dysfunction, interfere with coagulation pathways or modulate inflammatory phenomenon. Whether or not these new conveyors of biological information contribute to the acquisition and/or maintenance of the altered endothelial phenotype is unexplored in PH and requires further study. @ERSpublications Patients with PH have elevated circulating levels of microparticles which may contribute to disease pathophysiology

Robust Label-free, Quantitative Profiling of Circulating Plasma Microparticle (MP) Associated Proteins

“…Defining and quantifying the origin of MP in blood is key to characterize vascular diseases (5)(6)(7). FCM based profiling of MP origin is restricted to the use of one or two markers per cell type.…”

“…MP production starts with an increase in intracellular calcium, activation of calcium sensitive enzymes, cleavage of structural filaments, and formation of blebs on the surface of cells, which are finally shed off (2)(3)(4). MP are present in extracellular biological fluids and in plasma, where numbers were generally reported to increase under pathophysiological conditions (5)(6)(7). There is increasing evidence that MP are part of a sophisticated intercellular communication network and are involved in repair of damaged tissue (8,9).…”

Endothelial and Smooth Muscle Cell Interactions in the Pathobiology of Pulmonary Hypertension

“…Higher levels of endothelium-derived MPs bearing E-selectin are also noted in patients with thromboembolic PH as compared with subjects with nonthromboembolic PH (125), suggesting that the cause of the disease may influence MP levels (17). MPs are not only a biomarker of PH; they also actively contribute to the development of PH (126,127).…”

“…However, there is increasing evidence that the relationship between the EC and the SMC is not a simple one-way interaction from the endothelium to the SMC; rather, there are complicated interactions between them (9-11). Moreover, the communication patterns are not limited to paracrine signaling; cross-talk through myoendothelial gap junctions (MEJs), extracellular vesicles (EVs), and other mechanisms is critically involved (12)(13)(14)(15)(16)(17)(18)(19)(20). These mechanisms operate in a complicated but co-ordinated manner to maintain the homeostasis of the pulmonary circulation.…”

Microparticles and vascular dysfunction in obstructive sleep apnoea

“…However, MPs are more usually considered independent functional pathological effectors in a large variety of diseases, including cardiovascular and metabolic disorders such as coronary heart disease [27,28], hypertension [29] and diabetes [30], and severe pulmonary diseases such as acute lung injury [31] and pulmonary hypertension [32]. Furthermore, MPs that harbour markers of cellular activation have been shown to predict poor cardiovascular outcomes in at-risk patients [33,34].…”