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Journal of Lipid Research, Vol. 43, 1846-1854, November 2002
Copyright © 2002 by Lipid Research, Inc.

Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells

Marleen M. J. van Greevenbroek¹, Vicky M. M-J. Vermeulen and Tjerk W. A. de Bruin

Laboratory for Molecular Metabolism and Endocrinology, Maastricht University, Maastricht, The Netherlands

¹ To whom correspondence should be addressed. e-mail: m.vangreevenbroek{at}intmed.unimaas.nl

The aim of this study was to evaluate whether soluble factors in plasma of familial combined hyperlipidemia (FCHL) patients affect hepatic protein secretion. Cultured human hepatocytes, i.e., HepG2 cells, were incubated with fasting plasma (20%, v/v, in DMEM) from untreated FCHL patients or normolipidemic controls. Overall protein secretion was 10–15% higher after incubation with FCHL plasma. This was specifically caused by an increase in four secreted proteins, with estimated sizes of 240, 180, 120, and <40 kD (P < 0.001, P < 0.006, P < 0.002, P < 0.02, respectively). The 240 kD protein in the secretion proteome was identified as fibronectin by mass spectrometry. Plasma fibronectin concentrations were elevated in FCHL patients, confirming biological relevance of these data. Overall protein secretion by HepG2 cells correlated with concentrations of triglycerides (r = 0.61, P < 0.001) in the applied plasma samples. VLDL+IDL isolated from FCHL patients, induced a higher protein secretion than lipoproteins isolated from controls (P < 0.001). Remarkably, secretion of apoB, the structural protein of VLDL, was stimulated to a similar extent by FCHL and control plasma.

FCHL plasma did not induce excess secretion of apoB by HepG2 cells compared with control plasma. FCHL plasma did stimulate secretion of several distinct hepatic proteins, among which fibronectin was identified.

Abbreviations: CHD, coronary heart disease; CRE, cAMP response elements; FCHL, familial combined hyperlipidemia; FFA, free fatty acid

Supplementary key words hepatic lipoproteins fibronectin • HepG2 • familial combined hyperlipidemia • triglycerides

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