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Conjugated linoleic acid induces an atheroprotective macrophage MΦ2 phenotype and limits foam cell formation.

de Gaetano M, Alghamdi K, Marcone S, Belton O - J Inflamm (Lond) (2015)

Bottom Line: However, the exact mechanisms through which CLA mediates this effect remain to be elucidated.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.The data increases the understanding of the pathways regulated by CLA in atheroprotection, namely, inhibiting the progressive acquisition of a pro-inflammatory macrophage phenotype.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical and Biomolecular Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.

ABSTRACT

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.

Conclusion: The data increases the understanding of the pathways regulated by CLA in atheroprotection, namely, inhibiting the progressive acquisition of a pro-inflammatory macrophage phenotype.

No MeSH data available.


Related in: MedlinePlus

Potential atheroprotective mechanism of CLA on the macrophage/foam cell axis. (a) Th-1 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ1 macrophage pro-inflammatory phenotype. (b) Th-2 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ2 macrophage anti-inflammatory phenotype. (c) CLA action primes M-CSF-triggered monocyte differentiation towards an MΦ2-type macrophage. (d) In the presence of high levels of lipids in the extracellular matrix, CLA induces a dual mechanism PPARγ/LXRα-mediated (i-ii), by increasing CD36 levels (iii), allowing lipids to enter the cell (iv), and secondly, promoting cholesterol efflux, by increasing ABCA-1 mRNA expression (v), thus preventing lipid engulfment of the cell (vi), and the consequent foam cell formation. Moreover, CLA inhibits the secretion of pro-inflammatory cytokines (vii).
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Fig6: Potential atheroprotective mechanism of CLA on the macrophage/foam cell axis. (a) Th-1 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ1 macrophage pro-inflammatory phenotype. (b) Th-2 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ2 macrophage anti-inflammatory phenotype. (c) CLA action primes M-CSF-triggered monocyte differentiation towards an MΦ2-type macrophage. (d) In the presence of high levels of lipids in the extracellular matrix, CLA induces a dual mechanism PPARγ/LXRα-mediated (i-ii), by increasing CD36 levels (iii), allowing lipids to enter the cell (iv), and secondly, promoting cholesterol efflux, by increasing ABCA-1 mRNA expression (v), thus preventing lipid engulfment of the cell (vi), and the consequent foam cell formation. Moreover, CLA inhibits the secretion of pro-inflammatory cytokines (vii).

Mentions: In summary, the data provides a novel mechanism for CLA in atherosclerosis Figure 6. The atheroprotective c-9,t-11 isomer and the CLA blend negatively regulate expression of pro-inflammatory mediators via a PPARγ and LXRα dependent mechanism. As a consequence, differentiation process is shifted towards an anti-inflammatory MΦ2 phenotype, characterised by increased CD36 and ABCA-1 expression, thus preventing macrophage lipid engulfment and promoting cholesterol efflux towards exogenous acceptors.Figure 6


Conjugated linoleic acid induces an atheroprotective macrophage MΦ2 phenotype and limits foam cell formation.

de Gaetano M, Alghamdi K, Marcone S, Belton O - J Inflamm (Lond) (2015)

Potential atheroprotective mechanism of CLA on the macrophage/foam cell axis. (a) Th-1 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ1 macrophage pro-inflammatory phenotype. (b) Th-2 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ2 macrophage anti-inflammatory phenotype. (c) CLA action primes M-CSF-triggered monocyte differentiation towards an MΦ2-type macrophage. (d) In the presence of high levels of lipids in the extracellular matrix, CLA induces a dual mechanism PPARγ/LXRα-mediated (i-ii), by increasing CD36 levels (iii), allowing lipids to enter the cell (iv), and secondly, promoting cholesterol efflux, by increasing ABCA-1 mRNA expression (v), thus preventing lipid engulfment of the cell (vi), and the consequent foam cell formation. Moreover, CLA inhibits the secretion of pro-inflammatory cytokines (vii).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4340802&req=5

Fig6: Potential atheroprotective mechanism of CLA on the macrophage/foam cell axis. (a) Th-1 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ1 macrophage pro-inflammatory phenotype. (b) Th-2 cytokine environment primes M-CSF-triggered monocyte differentiation towards an MΦ2 macrophage anti-inflammatory phenotype. (c) CLA action primes M-CSF-triggered monocyte differentiation towards an MΦ2-type macrophage. (d) In the presence of high levels of lipids in the extracellular matrix, CLA induces a dual mechanism PPARγ/LXRα-mediated (i-ii), by increasing CD36 levels (iii), allowing lipids to enter the cell (iv), and secondly, promoting cholesterol efflux, by increasing ABCA-1 mRNA expression (v), thus preventing lipid engulfment of the cell (vi), and the consequent foam cell formation. Moreover, CLA inhibits the secretion of pro-inflammatory cytokines (vii).
Mentions: In summary, the data provides a novel mechanism for CLA in atherosclerosis Figure 6. The atheroprotective c-9,t-11 isomer and the CLA blend negatively regulate expression of pro-inflammatory mediators via a PPARγ and LXRα dependent mechanism. As a consequence, differentiation process is shifted towards an anti-inflammatory MΦ2 phenotype, characterised by increased CD36 and ABCA-1 expression, thus preventing macrophage lipid engulfment and promoting cholesterol efflux towards exogenous acceptors.Figure 6

Bottom Line: However, the exact mechanisms through which CLA mediates this effect remain to be elucidated.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.The data increases the understanding of the pathways regulated by CLA in atheroprotection, namely, inhibiting the progressive acquisition of a pro-inflammatory macrophage phenotype.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical and Biomolecular Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.

ABSTRACT

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.

Conclusion: The data increases the understanding of the pathways regulated by CLA in atheroprotection, namely, inhibiting the progressive acquisition of a pro-inflammatory macrophage phenotype.

No MeSH data available.


Related in: MedlinePlus