Plasma distribution of apolipoprotein A-IV in patients with coronary artery disease and healthy controls

Benjie Ezeh, Marina Haiman, Hannes F. Alber, Birgit Kunz, Bernhard Paulweber, Arno Lingenhel, Hans-Georg Kraft, Franz Weidinger, Otmar Pachinger, Hans Dieplinger, and Florian Kronenberg

Inst. Med. Biol. Human Genetics, University of Innsbruck, Innsbruck A-6020

Corresponding Author: Florian.Kronenberg{at}uibk.ac.at

Recent studies observed lower apolipoprotein A-IV (apoA IV) plasma concentrations in patients with coronary artery disease (CAD). The actual distribution of the anti-atherogenic apoA IV in human plasma, however, is discussed controversially and it was never investigated in CAD patients. We therefore developed a new and gentle technique to separate the various apoA IV-containing plasma fractions. Using a combination of precipitation of all lipoproteins with 40% phosphotungstic acid (PTA, pH=7.6) and 4M MgCl2 on the one hand and immunoprecipitation of all apoA I-containing particles with an anti-apoA I antibody on the other hand, we obtained three fractions of apoA IV: lipid-free apoA IV (about 4% of total apoA IV), apoA-IV associated with apoA-I (LpA-I:A-IV, 12%) and apoA I-unbound but lipoprotein-containing apoA IV (LpA-IV, 84%). Finally, we compared these three apoA IV fractions between 52 patients with a history of CAD and 52 age- and sex-matched healthy controls. Patients had significantly lower apoA IV levels when compared to controls (10.28+-3.67 vs. 11.85+-2.82 mg/dl, p=0.029). However, we observed no major differences for the three plasma apoA-IV fractions between patients and controls. We conclude that the use of a gentle method to separate the various apoA IV-containing plasma fractions reveals a different distribution of apoA IV than in many earlier studies. Furthermore, there exist no major differences in the apoA IV plasma distribution pattern between CAD patients and controls. Therefore, the anti-atherogenic effect of apoA IV has to be explained by other functional properties of apoA IV (e.g. the antioxidative characteristics).

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