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Targeting oxidized LDL improves insulin sensitivity and immune cell function in obese Rhesus macaques.

Abstract
Oxidation of LDL (oxLDL) is a crucial step in the development of cardiovascular disease. Treatment with antibodies directed against oxLDL can reduce atherosclerosis in rodent models through unknown mechanisms. We demonstrate that through a novel mechanism of immune complex formation and Fc-γ receptor (FcγR) engagement, antibodies targeting oxLDL (MLDL1278a) are anti-inflammatory on innate immune cells via modulation of Syk, p38 MAPK phosphorylation and NFκB activity. Subsequent administration of MLDL1278a in diet-induced obese (DIO) nonhuman primates (NHP) resulted in a significant decrease in pro-inflammatory cytokines and improved overall immune cell function. Importantly, MLDL1278a treatment improved insulin sensitivity independent of body weight change. This study demonstrates a novel mechanism by which an anti-oxLDL antibody improves immune function and insulin sensitivity independent of internalization of oxLDL. This identifies MLDL1278a as a potential therapy for reducing vascular inflammation in diabetic conditions.
AuthorsShijie Li, Paul Kievit, Anna-Karin Robertson, Ganesh Kolumam, Xiumin Li, Karin von Wachenfeldt, Christine Valfridsson, Sherry Bullens, Ilhem Messaoudi, Lindsay Bader, Kyra J Cowan, Amrita Kamath, Nicholas van Bruggen, Stuart Bunting, Björn Frendéus, Kevin L Grove
JournalMolecular metabolism (Mol Metab) Vol. 2 Issue 3 Pg. 256-69 ( 2013) ISSN: 2212-8778 [Print] Germany
PMID24049738 (Publication Type: Journal Article)

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