© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Evidence That Lipoproteins Are Carriers of Bioactive Factors
From the Medizinische Universitäts-Poliklinik, Wilhelmstr. 35-37, Bonn, Germany.
Correspondence to Prof Dr A. Sachinidis, Medizinische Universitäts-Poliklinik, Wilhelmstr. 35-37, 53111 Bonn, Germany. E-mail sachinidis{at}uni-bonn.de
Abstract—We recently demonstrated that the mitogenic effect of LDL (100 µg/mL) as well as its early intracellular signaling pathway are mediated by a pertussis-toxin (PTX)-sensitive Gi protein-coupled receptor that is independent from its classical receptor and involves activation of extracellular response kinases (ERK1/2) (also known as p44mapk/p42mapk). In the present study we examined whether LDL-adherent factors may be responsible for some of the effects of LDL. The term "signaling activity" is used to characterize fractions that cause an increase in intracellular free Ca2+ concentration or stimulate ERK1/2 and c-fos mRNA expression. LDL, HDL, and VLDL stimulate ERK1/2 with the following order of potency: LDL>HDL>VLDL. After delipidation of LDL with chloroform/methanol/water mixtures a PTX-sensitive signaling activity was found in one fraction arbitrarily called LDL-F. After further analysis of LDL-F compounds by high pressure liquid chromatography, a PTX-sensitive signaling activity was detected only in the fraction with a retention time of 33 minutes (arbitrarily called LDL-F33). Similarly, after separation of sphingosine-1–phosphate (SPP) and sphingosylphosphorylcholine (SPC) by high pressure liquid chromatography, a PTX-sensitive signaling activity was found in the fractions 33 and 33 to 35, respectively. These findings demonstrate that the effects of LDL-F33 are mimicked by similar fractions collected from SPP/SPC, hence suggesting that these LDL-adherent molecules are possibly closely related to SPP/SPC. A PTX-sensitive signaling activity was also detected in HDL and HDL-F33. Therefore, LDL and other lipoproteins may function as carriers for bioactive phospholipids thereby contributing to the development of coronary artery disease. Our findings support a new research concept that may contribute in elucidating cellular mechanisms promoting coronary artery disease.
Key Words: lipoproteins • vascular smooth muscle cells • MAP kinases • pertussis toxin
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