Abstract
Here, we review current data elucidating the role of red blood cell derived microparticles (RMPs) in normal vascular physiology and disease progression. Microparticles (MPs) are submicron-size, membrane-encapsulated vesicles derived from various parent cell types. MPs are produced in response to numerous stimuli that promote a sequence of cytoskeletal and membrane phospholipid changes and resulting MP genesis. MPs were originally considered as potential biomarkers for multiple disease processes and more recently are recognized to have pleiotropic biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in initiating apoptosis. RMPs, specifically, form normally during RBC maturation in response to injury during circulation, and are copiously produced during processing and storage for transfusion. Notably, several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs markedly from that of intact RBCs and the nature/composition of RMP components are affected by the specific circumstances of RMP genesis. Described RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion as well as influence upon vasoregulation via influence upon nitric oxide (NO) bioavailability. Of particular relevance, RMPs scavenge NO more avidly than do intact RBCs; this physiology has been proposed to contribute to the impaired oxygen delivery homeostasis that may be observed following transfusion. In summary, RMPs are submicron particles released from RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in normal and patho-physiology and in transfusion recipients is an area of continued investigation.
Highlights
red blood cell derived microparticles (RMPs) half-life in this model was observed to be ∼15–20 min, which is consistent with the time course for blood pressure changes that occur with infusion of stored RED BLOOD CELL (RBC) supernatants (Donadee et al, 2011)
MPs are submicron particles that originate from varied cell populations, that form in response to a multitude of stimuli through cell membrane re-organization, blebbing and shedding
RMP production accelerates during RBC storage due to associated biochemical changes: increased cytosolic calcium, ATP depletion, FIGURE 7 | Vasoactivity of infused packed red cell supernatant/plasma. (A) Experimental time line for packed red cell supernatant infusions
Summary
MP formation is enhanced by stress and injury and MPs have been considered as potential biomarkers for disease onset and progression. MP levels, in particular: for platelet-, leukocyte-, and endothelium-related MPs, are known to increase in the setting of vascular injury, pro-thrombotic and pro-inflammatory states that complicate a broad array of health conditions, such as diabetes (Feng et al, 2010), pulmonary hypertension (Forest et al, 2010), chronic kidney disease (Faure et al, 2006), preeclampsia (González-Quintero et al, 2003), atherosclerosis (Bernal-Mizrachi et al, 2003), and heart failure (Amabile et al, 2012) amongst others
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