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Enhanced Lipoprotein Lipase Secretion and Foam Cell Formation by Macrophages of Patients with Growth Hormone Deficiency: Possible Contribution to Increased Risk of Atherogenesis?

Centre Hospitalier de l’Université de Montréal Research Centre, Notre-Dame Hospital, and Department of Nutrition, University of Montreal, Montreal, Canada H2L 4M1

Address all correspondence and requests for reprints to: Dr. Geneviève Renier, Centre Hospitalier de l’Université de Montréal Research Centre, Notre-Dame Hospital, 3rd floor, J. A. de Sève, Y-3622, 1560 Sherbrooke Street East, Montreal, Québec, Canada H2L 4M1. E-mail: genevieve.renier{at}umontreal.ca.

GH deficiency is associated with increased prevalence of atherosclerosis, and recent data indicate a proatherogenic role for macrophage lipoprotein lipase (LPL) in the arterial wall. In this pilot study, we determined LPL expression and foam cell formation in monocyte-derived macrophages of 12 control subjects and nine patients with GH deficiency without GH replacement therapy. LPL mRNA levels, mass, and activity were increased in macrophages of patients with GH deficiency. In these subjects, macrophage LPL activity correlated with body mass index and fat mass. Incubation of patient macrophages with IGF-I for 24 h or differentiation of monocytes isolated from GH-deficient patients into macrophages in the presence of this growth factor decreased the amount of LPL mass. Compared with control cells, macrophages derived from GH-deficient patients took up and stored increased amounts of proatherogenic lipoproteins and were more easily converted to foam cells. In the supernatants of these cells, increased levels of free fatty acids and TNF were also documented. These results demonstrate that macrophages of patients with GH deficiency secrete increased amounts of proatherogenic cytokines and are more susceptible to foam cell formation. These alterations may contribute to the increased cardiovascular risk in patients with GH deficiency.

This work was supported in part by Eli Lilly.

Abbreviations: BMI, Body mass index; Dil, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LDL, low-density lipoprotein; LPL, lipoprotein lipase; oxLDL, oxidized LDL.

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