Conjugated linoleic acid induces an atheroprotective macrophage MΦ2 phenotype and limits foam cell formation.
BACKGROUND
Atherosclerosis, the underlying cause of heart attack and strokes, is a progresive dyslipidemic and inflammatory disease where monocyte-derived macrophage cells play a pivotal role. Although most of the mechanisms that contribute to the progression of atherosclerosis have been identified, there is limited information on those governing regression. Conjugated linoleic acid (CLA) is a group of isomers of linoleic acid that differ in the position and/or geometry of their double bonds. We have previously shown that a specific CLA blend (80:20 cis-9,trans-11:trans-10,cis-12-CLA) induces regression of pre-established atherosclerosis in vivo, via modulation of monocyte/macrophage function. However, the exact mechanisms through which CLA mediates this effect remain to be elucidated.


METHODS
Here, we address if CLA primes monocytes towards an anti-inflammatory MΦ2 macrophage and examine the effect of individual CLA isomers and the atheroprotective blend on monocyte-macrophage differentiation, cytokine generation, foam cell formation and cholesterol metabolism in human peripheral blood monocyte (HPBMC)-derived macrophages.


RESULTS
cis-9,trans-11-CLA and the atheroprotective 80:20 CLA blend regulates expression of pro-inflammatory mediators and modulates the inflammatory cytokine profile of macrophages and foam cells. In addition, cis-9,trans-11-CLA and CLA blend primes HPBMCs towards an anti-inflammatory MΦ2 phenotype, characterised by increased scavenger receptor (CD36) and efflux protein (ABCA-1) expression. Furthermore, this altered macrophage phenotype impacts on foam cell formation, inhibiting ox-LDL accumulation and promoting cholesterol efflux via both PPARγ and LXRα dependent pathways.


CONCLUSIONS
The data increases the understanding of the pathways regulated by CLA in atheroprotection, namely, inhibiting the progressive acquisition of a pro-inflammatory macrophage phenotype.
School of Biomedical and Biomolecular Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
Monica
M
de Gaetano
School of Biomedical and Biomolecular Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
Kawthar
K
Alghamdi
School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
Simone
S
Marcone
School of Biomedical and Biomolecular Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
Orina
O
Belton
Atherosclerosis; Cholesterol efflux; Conjugated linoleic acid; Foam cell formation; Macrophage differentiation; Scavenger receptors