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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: Conjugated linoleic acid (CLA) is a group of isomers of linoleic acid that differ in the position and/or geometry of their double bonds.However, the exact mechanisms through which CLA mediates this effect remain to be elucidated.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.

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: Conjugated linoleic acid (CLA) is a group of isomers of linoleic acid that differ in the position and/or geometry of their double bonds.However, the exact mechanisms through which CLA mediates this effect remain to be elucidated.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.

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