Lipoprotein-apheresis reduces circulating microparticles in individuals with familial hypercholesterolemia

David A Price,Dev B.N Datta,Elizabeth A Ellins,Irina A Guschina,Gareth R Willis,Katherine D Connolly,Kristin Ladell,D Aled Rees,Philip E James

doi:10.1194/jlr.m049726

David A Price, Dev B.N Datta + Show 7 more

Open Access

https://doi.org/10.1194/jlr.m049726

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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.

Highlights

Lipoprotein-apheresis removes LDLcholesterol in patients with severe dyslipidemia
MP size and concentration pre- versus post-apheresis Two techniques, tunable resistive pulse sensing (TRPS) and nanoparticle tracking analysis (NTA), were used to analyze MP size and concentration; the detectability was compared for each technique pre- and post-apheresis
The present study shows novel data regarding the effects of apheresis on MP size, concentration, TABLE 2

Summary

Introduction

Lipoprotein-apheresis (apheresis) removes LDLcholesterol in patients with severe dyslipidemia. 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.—Connolly, K. In severe forms of FH, diet alteration and lipid lowering medications are often insufficient to lower LDL levels enough to abate atherosclerotic plaque formation [3]. These patients require frequent (bi-weekly) lipoprotein-apheresis (hereafter referred to as “apheresis”) treatments in combination with dietary and pharmacological intervention to control LDL levels [4].

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