Generation in human plasma of misfolded, aggregation-prone electronegative low density lipoprotein

Giulia Greco, Gabor Balogh, Roberto Brunelli, Graziella Costa, Marco De Spirito, Laura Lenzi, Giampiero Mei, Fulvio Ursini, Tiziana Parasassi

Research output: Contribution to journalArticle

21 Citations (Scopus)

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°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.

Original languageEnglish
Pages (from-to)628-635
Number of pages8
JournalBiophysical Journal
Volume97
Issue number2
DOIs
Publication statusPublished - 2009

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LDL Lipoproteins
Lipids
Apoproteins
Secretory Phospholipase A2
Lysophospholipids
oxidized low density lipoprotein
Lipolysis
Nonesterified Fatty Acids
Anions
Chromatography
Atherosclerosis
Proteins
Cardiovascular Diseases
Calcium

ASJC Scopus subject areas

  • Biophysics

Cite this

Generation in human plasma of misfolded, aggregation-prone electronegative low density lipoprotein. / Greco, Giulia; Balogh, Gabor; Brunelli, Roberto; Costa, Graziella; De Spirito, Marco; Lenzi, Laura; Mei, Giampiero; Ursini, Fulvio; Parasassi, Tiziana.

In: Biophysical Journal, Vol. 97, No. 2, 2009, p. 628-635.

Research output: Contribution to journalArticle

Greco, G, Balogh, G, Brunelli, R, Costa, G, De Spirito, M, Lenzi, L, Mei, G, Ursini, F & Parasassi, T 2009, 'Generation in human plasma of misfolded, aggregation-prone electronegative low density lipoprotein', Biophysical Journal, vol. 97, no. 2, pp. 628-635. https://doi.org/10.1016/j.bpj.2009.05.005
Greco, Giulia ; Balogh, Gabor ; Brunelli, Roberto ; Costa, Graziella ; De Spirito, Marco ; Lenzi, Laura ; Mei, Giampiero ; Ursini, Fulvio ; Parasassi, Tiziana. / Generation in human plasma of misfolded, aggregation-prone electronegative low density lipoprotein. In: Biophysical Journal. 2009 ; Vol. 97, No. 2. pp. 628-635.
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