Plasma factors controlling atrial natriuretic peptide (ANP) aggregation: role of lipoproteins

We have previously shown that human plasma atrial a-natriuretic peptide (al pha -hANP) sequestering is a protective phenomenon against amyloid aggregat ion. In the present work, the possible role of lipoproteins as alpha -hANP binding factors has been investigated in vitro using an experimental model, developed in our laboratory, that allows to work at physiological concentr ations. This approach consists of gel filtration on Sephacryl S-300 HR of b ig alpha-[I-125]hANP generated in phosphate buffered saline or in human nor mal plasma supplemented or not with lipoproteins. The results of these expe riments indicate that high density lipoproteins (HDL) are responsible for t he ANP binding phenomenon observed in vitro, while low density lipoproteins and very low density lipoproteins do not directly interact with ANP. Moreo ver, the HDL remodeling process occurring in vitro has been analyzed during plasma incubation by monitoring the redistribution of lipids and apolipopr oteins among the HDL subclasses. The changes in HDL size and composition ob served in incubated plasma were compared with the redistribution of endogen ous and labeled big ANP. The obtained results revealed that both tend to fo llow the molecular rearrangement in plasma of apolipoprotein A-I containing particles and suggested that, among HDL species, the small particles are m ainly involved in the ANP binding phenomenon. This hypothesis was further d emonstrated by ligand blotting experiments that confirmed the existence of differences in the ability of HDL particles to bind alpha-[I-125]hANP. (C) 2001 Elsevier Science B.V. All rights reserved.