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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

Composition of plaques. (A-D) Relative macrophage and smooth muscle cell content did not change in plaques from mice subjected to the combination of surgery and blood loss (double hit). (A,C) Macrophages (CD68) and (B,D) vascular smooth muscle cells (VSMCs; α-smooth muscle actin) were stained by immunofluorescence, and relative areas staining positive for the respective antigens were morphometrically determined. No significant change of the relative contribution of VSMC or macrophages to the larger lesions was detected when double hit was inflicted. Kruskal–Wallis test, sham n=3; surgery n=4; bleed n=7; double hit n=8; n varies due to differential presence of measureable lesions in groups, P=n.s. (E) Collagen content was very low in the plaques and distribution signatures did not overtly differ between groups. (F) Polymorphonuclear (PMN) cell recruitment to the plaques was low. Mainly, PMNs were located in the subendothelial areas likely owing to the acute recruitment of myeloid cells as outlined in the text. (G) T-cell recruitment was mainly observed in the adventitia. Within the plaques, T cells were extremely rare. (H) To assess whether differences in leukocyte proliferation could be responsible for differences in leukocyte content, proliferating cell nuclear antigen (PCNA) was stained. No differences between the groups were detected. Proliferation in the plaques was extremely rare. Arrows indicate typical areas with antigen positive staining.
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DMM018713F3: Composition of plaques. (A-D) Relative macrophage and smooth muscle cell content did not change in plaques from mice subjected to the combination of surgery and blood loss (double hit). (A,C) Macrophages (CD68) and (B,D) vascular smooth muscle cells (VSMCs; α-smooth muscle actin) were stained by immunofluorescence, and relative areas staining positive for the respective antigens were morphometrically determined. No significant change of the relative contribution of VSMC or macrophages to the larger lesions was detected when double hit was inflicted. Kruskal–Wallis test, sham n=3; surgery n=4; bleed n=7; double hit n=8; n varies due to differential presence of measureable lesions in groups, P=n.s. (E) Collagen content was very low in the plaques and distribution signatures did not overtly differ between groups. (F) Polymorphonuclear (PMN) cell recruitment to the plaques was low. Mainly, PMNs were located in the subendothelial areas likely owing to the acute recruitment of myeloid cells as outlined in the text. (G) T-cell recruitment was mainly observed in the adventitia. Within the plaques, T cells were extremely rare. (H) To assess whether differences in leukocyte proliferation could be responsible for differences in leukocyte content, proliferating cell nuclear antigen (PCNA) was stained. No differences between the groups were detected. Proliferation in the plaques was extremely rare. Arrows indicate typical areas with antigen positive staining.

Mentions: We then questioned whether plaque composition was altered by perioperative stress and whether smooth muscle cells or macrophages increased preferentially due to the double hit. Macrophage and smooth-muscle-cell markers CD68 and αSMA were therefore assessed. Both CD68 and αSMA content of the plaque, as assessed by the relative area occupied by the respective antigens, remained unchanged by the double-hit intervention (Fig. 3A-D). To further assess differences in plaque composition, collagen was stained. A very inhomogeneous collagen signature and distribution was observed. No qualitative differences were detected (Fig. 3E). To further detail cellular composition, T cells and polymorphonuclear (PMN) cells were stained, showing rather sparse detection of these cell types (Fig. 3F,G). T cells were mainly detectable in the adventitia, whereas PMN-reactive materials were detected in the outer-most layer of the plaques with no differences between sham and double hit. To exclude that local proliferation of macrophages was affected by the interventions, proliferating cell nuclear antigen (PCNA) was stained (Fig. 3H). A very low frequency of proliferating cells was detected in the macrophage-laden plaque areas with likewise no difference between sham and double hit. We concluded that plaque composition was not majorly affected by the double hit and questioned whether plaque stability could still be altered.Fig. 3.


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)

Composition of plaques. (A-D) Relative macrophage and smooth muscle cell content did not change in plaques from mice subjected to the combination of surgery and blood loss (double hit). (A,C) Macrophages (CD68) and (B,D) vascular smooth muscle cells (VSMCs; α-smooth muscle actin) were stained by immunofluorescence, and relative areas staining positive for the respective antigens were morphometrically determined. No significant change of the relative contribution of VSMC or macrophages to the larger lesions was detected when double hit was inflicted. Kruskal–Wallis test, sham n=3; surgery n=4; bleed n=7; double hit n=8; n varies due to differential presence of measureable lesions in groups, P=n.s. (E) Collagen content was very low in the plaques and distribution signatures did not overtly differ between groups. (F) Polymorphonuclear (PMN) cell recruitment to the plaques was low. Mainly, PMNs were located in the subendothelial areas likely owing to the acute recruitment of myeloid cells as outlined in the text. (G) T-cell recruitment was mainly observed in the adventitia. Within the plaques, T cells were extremely rare. (H) To assess whether differences in leukocyte proliferation could be responsible for differences in leukocyte content, proliferating cell nuclear antigen (PCNA) was stained. No differences between the groups were detected. Proliferation in the plaques was extremely rare. Arrows indicate typical areas with antigen positive staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

DMM018713F3: Composition of plaques. (A-D) Relative macrophage and smooth muscle cell content did not change in plaques from mice subjected to the combination of surgery and blood loss (double hit). (A,C) Macrophages (CD68) and (B,D) vascular smooth muscle cells (VSMCs; α-smooth muscle actin) were stained by immunofluorescence, and relative areas staining positive for the respective antigens were morphometrically determined. No significant change of the relative contribution of VSMC or macrophages to the larger lesions was detected when double hit was inflicted. Kruskal–Wallis test, sham n=3; surgery n=4; bleed n=7; double hit n=8; n varies due to differential presence of measureable lesions in groups, P=n.s. (E) Collagen content was very low in the plaques and distribution signatures did not overtly differ between groups. (F) Polymorphonuclear (PMN) cell recruitment to the plaques was low. Mainly, PMNs were located in the subendothelial areas likely owing to the acute recruitment of myeloid cells as outlined in the text. (G) T-cell recruitment was mainly observed in the adventitia. Within the plaques, T cells were extremely rare. (H) To assess whether differences in leukocyte proliferation could be responsible for differences in leukocyte content, proliferating cell nuclear antigen (PCNA) was stained. No differences between the groups were detected. Proliferation in the plaques was extremely rare. Arrows indicate typical areas with antigen positive staining.
Mentions: We then questioned whether plaque composition was altered by perioperative stress and whether smooth muscle cells or macrophages increased preferentially due to the double hit. Macrophage and smooth-muscle-cell markers CD68 and αSMA were therefore assessed. Both CD68 and αSMA content of the plaque, as assessed by the relative area occupied by the respective antigens, remained unchanged by the double-hit intervention (Fig. 3A-D). To further assess differences in plaque composition, collagen was stained. A very inhomogeneous collagen signature and distribution was observed. No qualitative differences were detected (Fig. 3E). To further detail cellular composition, T cells and polymorphonuclear (PMN) cells were stained, showing rather sparse detection of these cell types (Fig. 3F,G). T cells were mainly detectable in the adventitia, whereas PMN-reactive materials were detected in the outer-most layer of the plaques with no differences between sham and double hit. To exclude that local proliferation of macrophages was affected by the interventions, proliferating cell nuclear antigen (PCNA) was stained (Fig. 3H). A very low frequency of proliferating cells was detected in the macrophage-laden plaque areas with likewise no difference between sham and double hit. We concluded that plaque composition was not majorly affected by the double hit and questioned whether plaque stability could still be altered.Fig. 3.

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