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Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition.

Janssen H, Wagner CS, Demmer P, Callies S, Sölter G, Loghmani-khouzani H, Hu N, Schuett H, Tietge UJ, Warnecke G, Larmann J, Theilmeier G - Dis Model Mech (2015)

Bottom Line: SAA levels peaked at 24 h (n=4, P<0.01).Relative VSMC and macrophage content remained unchanged.IL-6-inhibition or atorvastatin, but not blocking of IL-6 trans-signaling, significantly decreased plaque volume and complexity (n=8, P<0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, Germany Department of Anesthesiology, University of Heidelberg, 69120 Heidelberg, Germany.

No MeSH data available.


Related in: MedlinePlus

Signs precedingrupture of plaques were detected in animals exposed to the combination of surgery and blood loss (double hit). (A) A small proportion of lesions in control, but a large proportion of mice exposed to the double hit, demonstrated necrotic areas in the core of the plaque. Such necrosis had to be detectable on at least 50% of the sections to score 1 point. (B) Hemorrhage in the plaque was detected on H&E staining by the presence of red blood cells in the center of the lesion (arrowheads). Signs for intraplaque bleeding had to be present on at least 10% of the analyzed sections that span the whole innominate artery. (C) Buried fibrous caps were defined as αSMA-positive streaks (white arrowheads) that had been overgrown by new plaque material and were interpreted as buried fibrous caps secondary to plaque rupture, reorganization and overgrowth by plaque material. (D) Scoring of the features depicted in A-C with one point each revealed the presence of complex lesions in 60% of the double-hit mice, whereas control mice only had one feature in 32% of the cases, which mostly represented necrotic areas as shown in A. Fisher's exact test, sham, double hit n=8; surgery n=7; bleed n=5; **P<0.01 vs SHAM.
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DMM018713F4: Signs precedingrupture of plaques were detected in animals exposed to the combination of surgery and blood loss (double hit). (A) A small proportion of lesions in control, but a large proportion of mice exposed to the double hit, demonstrated necrotic areas in the core of the plaque. Such necrosis had to be detectable on at least 50% of the sections to score 1 point. (B) Hemorrhage in the plaque was detected on H&E staining by the presence of red blood cells in the center of the lesion (arrowheads). Signs for intraplaque bleeding had to be present on at least 10% of the analyzed sections that span the whole innominate artery. (C) Buried fibrous caps were defined as αSMA-positive streaks (white arrowheads) that had been overgrown by new plaque material and were interpreted as buried fibrous caps secondary to plaque rupture, reorganization and overgrowth by plaque material. (D) Scoring of the features depicted in A-C with one point each revealed the presence of complex lesions in 60% of the double-hit mice, whereas control mice only had one feature in 32% of the cases, which mostly represented necrotic areas as shown in A. Fisher's exact test, sham, double hit n=8; surgery n=7; bleed n=5; **P<0.01 vs SHAM.

Mentions: If the double hit led to unstable plaques, more plaques would exhibit necrotic and hemorrhagic areas. The Stary score is commonly used for classification of plaque stability in human atherosclerosis. Stary divides lesions into six different groups by qualitative characteristics such as lipid content, hematoma and layers of fibromuscular tissue (see Table 2 for definitions) (Stary, 2000). We found plaques of group IV to VI mainly in animals exposed to the double hit, whereas mice in the sham, hemorrhage and surgery groups presented less complex plaques, in groups I through III. The Stary score does not, however, provide a sufficiently high resolution of differences in vulnerability, because it collects all complex plaques in class VI, where surface defects, thrombosis and hemorrhage are grouped together. Therefore, we additionally scored the individual components of the Stary score by separately rating the presence or absence of plaque necrosis, intraplaque hemorrhage and buried fibrous caps to generate a gradual score that is accessible to non-parametric statistical analysis. The most stable plaque would have neither necrosis, nor hemorrhage, nor buried fibrous caps (0 points), whereas the most complex lesion would contain all three features (3 points). Mice subjected to the double hit had significantly higher scores, reflecting significantly more complex plaques than sham animals (P<0.01) (Fig. 4A-D).Fig. 4.


Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition.

Janssen H, Wagner CS, Demmer P, Callies S, Sölter G, Loghmani-khouzani H, Hu N, Schuett H, Tietge UJ, Warnecke G, Larmann J, Theilmeier G - Dis Model Mech (2015)

Signs precedingrupture of plaques were detected in animals exposed to the combination of surgery and blood loss (double hit). (A) A small proportion of lesions in control, but a large proportion of mice exposed to the double hit, demonstrated necrotic areas in the core of the plaque. Such necrosis had to be detectable on at least 50% of the sections to score 1 point. (B) Hemorrhage in the plaque was detected on H&E staining by the presence of red blood cells in the center of the lesion (arrowheads). Signs for intraplaque bleeding had to be present on at least 10% of the analyzed sections that span the whole innominate artery. (C) Buried fibrous caps were defined as αSMA-positive streaks (white arrowheads) that had been overgrown by new plaque material and were interpreted as buried fibrous caps secondary to plaque rupture, reorganization and overgrowth by plaque material. (D) Scoring of the features depicted in A-C with one point each revealed the presence of complex lesions in 60% of the double-hit mice, whereas control mice only had one feature in 32% of the cases, which mostly represented necrotic areas as shown in A. Fisher's exact test, sham, double hit n=8; surgery n=7; bleed n=5; **P<0.01 vs SHAM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582096&req=5

DMM018713F4: Signs precedingrupture of plaques were detected in animals exposed to the combination of surgery and blood loss (double hit). (A) A small proportion of lesions in control, but a large proportion of mice exposed to the double hit, demonstrated necrotic areas in the core of the plaque. Such necrosis had to be detectable on at least 50% of the sections to score 1 point. (B) Hemorrhage in the plaque was detected on H&E staining by the presence of red blood cells in the center of the lesion (arrowheads). Signs for intraplaque bleeding had to be present on at least 10% of the analyzed sections that span the whole innominate artery. (C) Buried fibrous caps were defined as αSMA-positive streaks (white arrowheads) that had been overgrown by new plaque material and were interpreted as buried fibrous caps secondary to plaque rupture, reorganization and overgrowth by plaque material. (D) Scoring of the features depicted in A-C with one point each revealed the presence of complex lesions in 60% of the double-hit mice, whereas control mice only had one feature in 32% of the cases, which mostly represented necrotic areas as shown in A. Fisher's exact test, sham, double hit n=8; surgery n=7; bleed n=5; **P<0.01 vs SHAM.
Mentions: If the double hit led to unstable plaques, more plaques would exhibit necrotic and hemorrhagic areas. The Stary score is commonly used for classification of plaque stability in human atherosclerosis. Stary divides lesions into six different groups by qualitative characteristics such as lipid content, hematoma and layers of fibromuscular tissue (see Table 2 for definitions) (Stary, 2000). We found plaques of group IV to VI mainly in animals exposed to the double hit, whereas mice in the sham, hemorrhage and surgery groups presented less complex plaques, in groups I through III. The Stary score does not, however, provide a sufficiently high resolution of differences in vulnerability, because it collects all complex plaques in class VI, where surface defects, thrombosis and hemorrhage are grouped together. Therefore, we additionally scored the individual components of the Stary score by separately rating the presence or absence of plaque necrosis, intraplaque hemorrhage and buried fibrous caps to generate a gradual score that is accessible to non-parametric statistical analysis. The most stable plaque would have neither necrosis, nor hemorrhage, nor buried fibrous caps (0 points), whereas the most complex lesion would contain all three features (3 points). Mice subjected to the double hit had significantly higher scores, reflecting significantly more complex plaques than sham animals (P<0.01) (Fig. 4A-D).Fig. 4.

Bottom Line: SAA levels peaked at 24 h (n=4, P<0.01).Relative VSMC and macrophage content remained unchanged.IL-6-inhibition or atorvastatin, but not blocking of IL-6 trans-signaling, significantly decreased plaque volume and complexity (n=8, P<0.01).

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, Germany Department of Anesthesiology, University of Heidelberg, 69120 Heidelberg, Germany.

No MeSH data available.


Related in: MedlinePlus