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Atherosclerosis in ApoE-deficient mice progresses independently of the NLRP3 inflammasome.

Menu P, Pellegrin M, Aubert JF, Bouzourene K, Tardivel A, Mazzolai L, Tschopp J - Cell Death Dis (2011)

Bottom Line: The interleukin-1 (IL-1) family of cytokines has been implicated in the pathogenesis of atherosclerosis in previous studies.The NLRP3 inflammasome has recently emerged as a pivotal regulator of IL-1β maturation and secretion by macrophages.No differences in atherosclerosis progression, infiltration of plaques by macrophages, nor plaque stability and phenotype across the genotypes studied were found.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.

ABSTRACT
The interleukin-1 (IL-1) family of cytokines has been implicated in the pathogenesis of atherosclerosis in previous studies. The NLRP3 inflammasome has recently emerged as a pivotal regulator of IL-1β maturation and secretion by macrophages. Little is currently known about a possible role for the NLRP3 inflammasome in atherosclerosis progression in vivo. We generated ApoE-/- Nlrp3-/-, ApoE-/- Asc-/- and ApoE-/- caspase-1-/- double-deficient mice, fed them a high-fat diet for 11 weeks and subsequently assessed atherosclerosis progression and plaque phenotype. No differences in atherosclerosis progression, infiltration of plaques by macrophages, nor plaque stability and phenotype across the genotypes studied were found. Our results demonstrate that the NLRP3 inflammasome is not critically implicated in atherosclerosis progression in the ApoE mouse model.

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Plaque stability is unaltered in NLRP3 inflammasome-deficient ApoE−/− mice. Smooth muscle actin (SMA) staining of atherosclerotic plaques across the four indicated genotypes
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fig3: Plaque stability is unaltered in NLRP3 inflammasome-deficient ApoE−/− mice. Smooth muscle actin (SMA) staining of atherosclerotic plaques across the four indicated genotypes

Mentions: In patients suffering from atherosclerosis, over 60% of myocardial infarctions are caused by low-grade (<50%) coronary artery stenosis.8 Therefore, the sheer surface of atherosclerotic plaques is clinically less crucial than their stability. Plaque smooth muscle cell content, a marker of plaque stability, was quantified by anti-α-smooth muscle actin staining (Figure 3). Again, we found no significant differences between the four genotypes. Furthermore, plaque phenotype was similar in all mice, showing lesions in advanced stage (Table 1). Although ApoE−/− ASC−/− mice featured significantly lower levels of plaque layering and adventitial inflammation, this was offset by an increased prevalence of thinned fibrous cap, suggesting that, overall, the plaque phenotype was not decisively more or less favorable than controls (Table 1).


Atherosclerosis in ApoE-deficient mice progresses independently of the NLRP3 inflammasome.

Menu P, Pellegrin M, Aubert JF, Bouzourene K, Tardivel A, Mazzolai L, Tschopp J - Cell Death Dis (2011)

Plaque stability is unaltered in NLRP3 inflammasome-deficient ApoE−/− mice. Smooth muscle actin (SMA) staining of atherosclerotic plaques across the four indicated genotypes
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101814&req=5

fig3: Plaque stability is unaltered in NLRP3 inflammasome-deficient ApoE−/− mice. Smooth muscle actin (SMA) staining of atherosclerotic plaques across the four indicated genotypes
Mentions: In patients suffering from atherosclerosis, over 60% of myocardial infarctions are caused by low-grade (<50%) coronary artery stenosis.8 Therefore, the sheer surface of atherosclerotic plaques is clinically less crucial than their stability. Plaque smooth muscle cell content, a marker of plaque stability, was quantified by anti-α-smooth muscle actin staining (Figure 3). Again, we found no significant differences between the four genotypes. Furthermore, plaque phenotype was similar in all mice, showing lesions in advanced stage (Table 1). Although ApoE−/− ASC−/− mice featured significantly lower levels of plaque layering and adventitial inflammation, this was offset by an increased prevalence of thinned fibrous cap, suggesting that, overall, the plaque phenotype was not decisively more or less favorable than controls (Table 1).

Bottom Line: The interleukin-1 (IL-1) family of cytokines has been implicated in the pathogenesis of atherosclerosis in previous studies.The NLRP3 inflammasome has recently emerged as a pivotal regulator of IL-1β maturation and secretion by macrophages.No differences in atherosclerosis progression, infiltration of plaques by macrophages, nor plaque stability and phenotype across the genotypes studied were found.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.

ABSTRACT
The interleukin-1 (IL-1) family of cytokines has been implicated in the pathogenesis of atherosclerosis in previous studies. The NLRP3 inflammasome has recently emerged as a pivotal regulator of IL-1β maturation and secretion by macrophages. Little is currently known about a possible role for the NLRP3 inflammasome in atherosclerosis progression in vivo. We generated ApoE-/- Nlrp3-/-, ApoE-/- Asc-/- and ApoE-/- caspase-1-/- double-deficient mice, fed them a high-fat diet for 11 weeks and subsequently assessed atherosclerosis progression and plaque phenotype. No differences in atherosclerosis progression, infiltration of plaques by macrophages, nor plaque stability and phenotype across the genotypes studied were found. Our results demonstrate that the NLRP3 inflammasome is not critically implicated in atherosclerosis progression in the ApoE mouse model.

Show MeSH
Related in: MedlinePlus