Lipoprotein-apheresis reduces circulating microparticles in individuals with familial hypercholesterolemia.

Autor: Connolly KD; Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom., Willis GR; Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom., Datta DB; Lipid Unit, Llandough Hospital, Cardiff CF64 2XX, United Kingdom., Ellins EA; 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., Ladell K; Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom., Price DA; Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom., Guschina IA; School of Biosciences, Cardiff University, Cardiff CF10 3AX, United Kingdom., Rees DA; Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom., James PE; Institute of Molecular and Experimental Medicine School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.
Jazyk: angličtina
Zdroj: Journal of lipid research [J Lipid Res] 2014 Oct; Vol. 55 (10), pp. 2064-72. Date of Electronic Publication: 2014 Aug 13.
DOI: 10.1194/jlr.M049726
Abstrakt: 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.
(Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.)
Databáze: MEDLINE