Generation in human plasma of misfolded, aggregation-prone electronegative LDL (Articolo in rivista)

Type
Label
  • Generation in human plasma of misfolded, aggregation-prone electronegative LDL (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.bpj.2009.05.005 (literal)
Alternative label
  • Giulia Greco1; Gabor Balogh2; Roberto Brunelli3; Graziella Costa1; Marco De Spirito4; Laura Lenzi1; Giampiero Mei5; Fulvio Ursini6; Tiziana Parasassi1 (2009)
    Generation in human plasma of misfolded, aggregation-prone electronegative LDL
    in Biophysical journal (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Giulia Greco1; Gabor Balogh2; Roberto Brunelli3; Graziella Costa1; Marco De Spirito4; Laura Lenzi1; Giampiero Mei5; Fulvio Ursini6; Tiziana Parasassi1 (literal)
Pagina inizio
  • 628 (literal)
Pagina fine
  • 635 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 97 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 2 (literal)
Note
  • ISI Web of Science (WOS) (literal)
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Istituto di Neurobiologia e Medicina Molecolare, CNR, Rome, Italy; 2 Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary; 3 Dipartimento di Ostetricia e Ginecologia, Università di Roma Sapienza, Rome, Italy; 4 Istituto di Fisica, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, Rome, Italy; 5 Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Roma Tor Vergata, Rome, Italy 6 Dipartimento di Chimica Biologica, Università di Padova, Padua, Italy (literal)
Titolo
  • Generation in human plasma of misfolded, aggregation-prone electronegative LDL (literal)
Abstract
  • Human plasma contains small amounts of a low density lipoprotein in which apoprotein is misfolded. Originally identified and isolated by means of anion-exchange chromatography, this component was subsequently described as electronegative low density lipoprotein (LDL)(-), with increased concentrations associated with elevated cardiovascular disease risk. It has been recognized recently as the trigger of LDL amyloidogenesis, which produces aggregates similar to subendothelial droplets observed in vivo in early atherogenesis. Although LDL(-) has been produced in vitro through various manipulations, the mechanisms involved in its generation in vivo remain obscure. By using a more physiological model, we demonstrate spontaneous, sustained and noticeable production of LDL(-) during incubation of unprocessed human plasma at 37 degrees C. In addition to a higher fraction of amyloidogenic LDL(-), LDL purified from incubated plasma contains an increased level of lysophospholipids and free fatty acids; analysis of LDL lipids packing shows their loosening. As a result, during plasma incubation, lipid destabilization and protein misfolding take place, and aggregation-prone particles are generated. All these phenomena can be prevented by inhibiting calcium-dependent secretory phospholipases A2. Our plasma incubation model, without removal of reaction products, effectively shows a lipid-protein interplay in LDL, where lipid destabilization after lipolysis threatens the apoprotein's structure, which misfolds and becomes aggregation-prone. (literal)
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