Abstract
High density lipoproteins (HDL) mediate reverse cholesterol transport as well as the clearance of oxidation products or inflammatory mediators, thereby contributing to tissue integrity. The decrease in HDL in inflammation has been attributed to decreased lecithin:cholesterol acyltransferase activity, whereas the role of phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein has not been analyzed in detail. We have studied the activities of HDL-modifying proteins and the heterogeneity of HDL in healthy control subjects and three groups of postsurgery patients: no bacterial infection (group 1), bacterial focus and systemic inflammatory response (group 2), and severe sepsis (group 3). For all patients, a decrease in total HDL could be demonstrated, with a loss of mainly large, apolipoprotein A-I (apoA-I) HDL particles, an almost total loss of apoC-I, and an increase in apoE HDL (200–500 kDa), which did not contain significant amounts of apoA-I, apoA-II, or apoC-I. PLTP activity was increased in patients of groups 2 and 3, paralleled by a redistribution of PLTP into a population of small (120- to 200-kDa) particles, probably representing PLTP homodimers or lipid-complexed PLTP. In summary, the increase in apoE HDL and PLTP activity may improve the delivery of energy substrates and phospholipids to tissues that must maintain cellular membrane homeostasis under conditions of inflammatory stress. —Barlage, S., D. Fröhlich, A. Böttcher, M. Jauhiainen, H. P. Müller, F. Noetzel, G. Rothe, C. Schütt, R. P. Linke, K. J. Lackner, C. Ehnholm, and G. Schmitz. ApoE-containing high density lipoproteins and phospholipid transfer protein activity increase in patients with a systemic inflammatory response.
Highlights
High density lipoproteins (HDL) mediate reverse cholesterol transport as well as the clearance of oxidation products or inflammatory mediators, thereby contributing to tissue integrity
To further elucidate the mechanisms that contribute to the decrease in HDL seen during the acute-phase response, we determined, whether intensive care patients who met the criteria of systemic inflammatory response sydrome (SIRS) and bacterial infection or severe sepsis differed regarding HDL cholesterol concentration, distribution of HDL subpopulations, as well as the activity of HDL-remodeling enzymes and lipid transfer proteins, when compared with intensive care patients without infection or healthy control subjects
Several potential mechanisms for the decrease in lecithin:cholesterol acyltransferase (LCAT) activity in inflammation have been reported, such as regulatory effects of cytokines such as interleukin 2 (IL-2) [11], a reduced association of LCAT with HDL due to an altered lipid composition of the HDL particle [29], or due to the displacement of the LCAT activator apolipoprotein A-I (apoA-I) by SAA1/2 [12]
Summary
High density lipoproteins (HDL) mediate reverse cholesterol transport as well as the clearance of oxidation products or inflammatory mediators, thereby contributing to tissue integrity. Inflammatory mediators suppress LCAT expression and activity [11, 12] and, in addition, apoA-I, which is the principal activator of LCAT [13], is suggested to be displaced from the HDL particle by the acute-phase protein serum amyloid A (SAA) [14] Both the phospholipid transfer protein (PLTP) and the cholesteryl ester transfer protein (CETP) are known to have a major impact on the metabolism of HDL particles in healthy individuals, few data are available on their role during inflammation [15]. Both proteins belong to a family of homologous lipid transfer/LPSbinding proteins, which includes the LPS-binding protein (LBP) [16, 17], and, these proteins may link the metabolism of HDL to the clearance of lipid inflammatory mediators
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