Targeting Oxidized LDL Improves Insulin Sensitivity and Immune Cell Function in Obese Rhesus Macaques

Overview

Journal Mol Metab

Specialty Cell Biology

Date 2013 Sep 20

PMID 24049738

Citations 19

Authors

Shijie 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

Bjorn Frendeus

Kevin L Grove

Affiliations

Soon will be listed here.

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.

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