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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

High-dose statin therapy 3 days prior to and 3 days after surgery in mice exposed to the double hit, and IL-6 signaling pathway interception. Mice were treated with 80 mg/kg body weight/day atorvastatin, blocking antibodies against IL-6 or the selective inhibition of IL-6 trans-signaling by gp130-Fc by a single subcutaneous injection. (A) Total cholesterol (n=5; P<0.05), (B) IL-6 plasma levels (n=4; P<0.05) and (C) plaque volume (double hit n=8; atorvastatin n=9; P<0.05) decreased significantly under atorvastatin. Mann–Whitney U-test. (D) Plaque complexity as assessed by the score was likewise significantly reduced (Fisher's exact test, double hit n=8; atorvastatin n=9; P<0.05). (E) The blocking antibody against IL-6 reduced plaque volume, whereas the selective inhibition of IL-6 trans-signaling by gp130-Fc did not yield any reduction in plaque volume. Mann–Whitney U-test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; P<0.05. (F) Plaque complexity was reduced by blocking antibody (Fisher's exact test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; **P<0.05 vs double hit).
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DMM018713F5: High-dose statin therapy 3 days prior to and 3 days after surgery in mice exposed to the double hit, and IL-6 signaling pathway interception. Mice were treated with 80 mg/kg body weight/day atorvastatin, blocking antibodies against IL-6 or the selective inhibition of IL-6 trans-signaling by gp130-Fc by a single subcutaneous injection. (A) Total cholesterol (n=5; P<0.05), (B) IL-6 plasma levels (n=4; P<0.05) and (C) plaque volume (double hit n=8; atorvastatin n=9; P<0.05) decreased significantly under atorvastatin. Mann–Whitney U-test. (D) Plaque complexity as assessed by the score was likewise significantly reduced (Fisher's exact test, double hit n=8; atorvastatin n=9; P<0.05). (E) The blocking antibody against IL-6 reduced plaque volume, whereas the selective inhibition of IL-6 trans-signaling by gp130-Fc did not yield any reduction in plaque volume. Mann–Whitney U-test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; P<0.05. (F) Plaque complexity was reduced by blocking antibody (Fisher's exact test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; **P<0.05 vs double hit).

Mentions: Statin treatment has been demonstrated to reduce perioperative cardiovascular events in patients at risk (Liakopoulos et al., 2008). To assess whether atorvastatin would exert similar effects in our model, we treated animals with high-dose statin or vehicle 3 days pre- and 3 days postoperatively as previously described (Larmann et al., 2013). Total cholesterol at the time of the double hit (P<0.05) and serum IL-6 level at the 6-h time point were decreased (P<0.05; Fig. 5A,B). Atorvastatin significantly reduced plaque volume compared to untreated animals (P<0.05; Fig. 5C). Lesions from statin-treated mice also reached significantly fewer points in the plaque score, indicating successful prevention of double-hit-induced plaque instability (P<0.05) (Fig. 5D).Fig. 5.


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)

High-dose statin therapy 3 days prior to and 3 days after surgery in mice exposed to the double hit, and IL-6 signaling pathway interception. Mice were treated with 80 mg/kg body weight/day atorvastatin, blocking antibodies against IL-6 or the selective inhibition of IL-6 trans-signaling by gp130-Fc by a single subcutaneous injection. (A) Total cholesterol (n=5; P<0.05), (B) IL-6 plasma levels (n=4; P<0.05) and (C) plaque volume (double hit n=8; atorvastatin n=9; P<0.05) decreased significantly under atorvastatin. Mann–Whitney U-test. (D) Plaque complexity as assessed by the score was likewise significantly reduced (Fisher's exact test, double hit n=8; atorvastatin n=9; P<0.05). (E) The blocking antibody against IL-6 reduced plaque volume, whereas the selective inhibition of IL-6 trans-signaling by gp130-Fc did not yield any reduction in plaque volume. Mann–Whitney U-test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; P<0.05. (F) Plaque complexity was reduced by blocking antibody (Fisher's exact test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; **P<0.05 vs double hit).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

DMM018713F5: High-dose statin therapy 3 days prior to and 3 days after surgery in mice exposed to the double hit, and IL-6 signaling pathway interception. Mice were treated with 80 mg/kg body weight/day atorvastatin, blocking antibodies against IL-6 or the selective inhibition of IL-6 trans-signaling by gp130-Fc by a single subcutaneous injection. (A) Total cholesterol (n=5; P<0.05), (B) IL-6 plasma levels (n=4; P<0.05) and (C) plaque volume (double hit n=8; atorvastatin n=9; P<0.05) decreased significantly under atorvastatin. Mann–Whitney U-test. (D) Plaque complexity as assessed by the score was likewise significantly reduced (Fisher's exact test, double hit n=8; atorvastatin n=9; P<0.05). (E) The blocking antibody against IL-6 reduced plaque volume, whereas the selective inhibition of IL-6 trans-signaling by gp130-Fc did not yield any reduction in plaque volume. Mann–Whitney U-test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; P<0.05. (F) Plaque complexity was reduced by blocking antibody (Fisher's exact test; double hit, gp130-Fc n=8; isotype n=5; IL-6 ab n=8; **P<0.05 vs double hit).
Mentions: Statin treatment has been demonstrated to reduce perioperative cardiovascular events in patients at risk (Liakopoulos et al., 2008). To assess whether atorvastatin would exert similar effects in our model, we treated animals with high-dose statin or vehicle 3 days pre- and 3 days postoperatively as previously described (Larmann et al., 2013). Total cholesterol at the time of the double hit (P<0.05) and serum IL-6 level at the 6-h time point were decreased (P<0.05; Fig. 5A,B). Atorvastatin significantly reduced plaque volume compared to untreated animals (P<0.05; Fig. 5C). Lesions from statin-treated mice also reached significantly fewer points in the plaque score, indicating successful prevention of double-hit-induced plaque instability (P<0.05) (Fig. 5D).Fig. 5.

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