title: 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.
authors.affiliation: Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Connolly
authors.affiliation: Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Willis
authors.affiliation: Lipid Unit, Llandough Hospital, Cardiff CF64 2XX, United Kingdom.
authors.forename: Dev B N
authors.initials: DB
authors.lastname: Datta
authors.affiliation: Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom Institute of Life Sciences, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ellins
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Guschina
authors.affiliation: Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: D Aled
authors.initials: DA
authors.lastname: Rees
authors.affiliation: Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
authors.forename: Philip E
authors.initials: PE
authors.lastname: James
mesh_terms: D000368:Aged; D001781:Blood Component Removal; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000628:therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D008078:Cholesterol, LDL
keywords: exosomes; extracellular vesicles; fatty acids; flow cytometry; low density lipoprotein-apheresis; microvesicles; nanoparticle tracking analysis; phosphatidylserine; tunable resistive pulse sensing