Lipoprotein-apheresis reduces circulating microparticles in individuals with familial hypercholesterolemia

Abstract

Lipoprotein-apheresis (apheresis) removes LDL-cholesterol in patients with severe dyslipidemia. However, reduction is transient, indicating that the long-term cardiovascular benefits of apheresis may not solely be due to LDL removal. Microparticles (MPs) are submicron vesicles released from the plasma membrane of cells. MPs, particularly platelet-derived MPs, are increasingly being linked to the pathogenesis of many diseases. We aimed to characterize the effect of apheresis on MP size, concentration, cellular origin, and fatty acid concentration in individuals with familial hypercholesterolemia (FH). Plasma and MP samples were collected from 12 individuals with FH undergoing routine apheresis. Tunable resistive pulse sensing (np200) and nanoparticle tracking analysis measured a fall in MP concentration (33 and 15%, respectively; P < 0.05) pre- to post-apheresis. Flow cytometry showed MPs were predominantly annexin V positive and of platelet (CD41) origin both pre- (88.9%) and post-apheresis (88.4%). Fatty acid composition of MPs differed from that of plasma, though apheresis affected a similar profile of fatty acids in both compartments, as measured by GC-flame ionization detection. MP concentration was also shown to positively correlate with thrombin generation potential. In conclusion, we show apheresis nonselectively removes annexin V-positive platelet-derived MPs in individuals with FH. These MPs are potent inducers of coagulation and are elevated in CVD; this reduction in pathological MPs could relate to the long-term benefits of apheresis.

Release and cellular origin of extracellular vesicles during circulation of whole blood over adsorbent polymers for lipid apheresis

“…MVs generated during lipid apheresis may either circulate as single vesicles or adhere to blood cells, to each other, or to the adsorbent polymers, as supported by recent clinical data from patients treated with different LDL apheresis systems, which showed a reduction of circulating MVs during lipid apheresis . As to their interaction with blood cells, we found that leukocytes, in particular monocytes, are the primary targets for MV adhesion, confirming that monocytes are central actors for MV clearance and suggesting that blood cells are not only donors, but also recipients of MVs in the circulation.…”

Cross-Talk between Lipoproteins and Inflammation: The Role of Microvesicles

“…In FH patients, plasma apheresis reduces circulating MV concentration, mainly platelet-derived MV AV + [88].…”

Platelet-derived vesicles: diagnostic and predictive value in cardiovascular diseases

“…Interestingly, the oxidative stress markers, such as plasma glutathione peroxidase and urinary 8-iso-prostaglandin F2 alpha, independently impacted on levels of platelet-derived vesicles [89] . Interestingly, the leptin can modulate platelet aggregation, shape platelet vesiculation and thereby links abdominal obesity and coagulopathy [90,91] . Moreover, leptin resistance rather than insulin resistance was found as a trigger for platelet activation that corresponds to increased risk of CV disease and CV events in patients with abdominal obesity, but not with diabetes mellitus [92,93] .…”