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Interleukin-17A contributes to the development of post-operative atrial fibrillation by regulating inflammation and fibrosis in rats with sterile pericarditis.

Fu XX, Zhao N, Dong Q, Du LL, Chen XJ, Wu QF, Cheng X, Du YM, Liao YH - Int. J. Mol. Med. (2015)

Bottom Line: Western blot analysis was applied to quantify the expression of IL-17A.Quantitative PCR was used to detect the mRNA expression of IL-17A, IL-6, IL-1β, transforming growth factor-β1 (TGF-β1), collagen type 1 (Col-1), collagen type 3 (Col-3) and α-smooth muscle actin (α-SMA).Gelatin zymography and reverse gelatin zymography were used to quantify the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs).

View Article: PubMed Central - PubMed

Affiliation: Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

ABSTRACT
Post-operative atrial fibrillation (AF) remains a common cause of morbidity. Increasing evidence indicates that inflammation and atrial fibrosis contribute to the pathogenesis of this condition. Interleukin (IL)-17A, a potent pro-inflammatory cytokine, has been implicated in the development of a number of cardiovascular diseases. However, its role in post-operative AF remains unknown. In the present study, sterile pericarditis (SP) was induced in rats by the epicardial application of sterile talc. AF was induced by transesophageal burst pacing. Western blot analysis was applied to quantify the expression of IL-17A. Quantitative PCR was used to detect the mRNA expression of IL-17A, IL-6, IL-1β, transforming growth factor-β1 (TGF-β1), collagen type 1 (Col-1), collagen type 3 (Col-3) and α-smooth muscle actin (α-SMA). Gelatin zymography and reverse gelatin zymography were used to quantify the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Histological analyses were performed to determine the extent of tissue inflammation and fibrosis. The rats with SP presented with a shorter refractoriness, a higher incidence and duration of AF, an enhanced susceptibility to developing AF, increased mRNA levels of AF-related pro-inflammatory cytokines (IL-6, IL-1β and TGF-β1), as well as marked atrial inflammation and fibrosis. The atrial IL-17A levels were elevated and correlated with the probability of developing AF. Treatment with anti-IL-17A monoclonal antibody decreased the levels of atrial IL-17A, prolonged refraction and markedly suppressed the development of AF. Simultaneously, inflammation and fibrosis were alleviated, which was further demonstrated by a decreased expression of AF-related pro-inflammatory cytokines, a downregulation in fibrosis-related mRNA expression (Col-1, Col-3 and α-SMA) and by the decreased activity of MMP-2/9 and TIMPs. Thus, the findings of our study indicate that IL-17A may play a pathogenic role in post-operative AF by inducing inflammation and fibrosis in rats with SP.

No MeSH data available.


Related in: MedlinePlus

Expression of atrial fibrillation (AF)-related pro-inflammatory cytokines at 4 days after surgery. (A) Fold mRNA expression of interleukin (IL)-6, IL-1β, transforming growth factor-β1 (TGF-β1) and IL-17A. (B) Protein expression of IL-17A detected by western blot analysis. (C) Quantitative analysis of IL-17A protein expression. *P<0.05 and **P<0.01 vs. Sham. #P<0.05 and ##P<0.01 vs. IgG2a. Sham, sham-operated rats; SP, rats with sterile pericarditis.
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f6-ijmm-36-01-0083: Expression of atrial fibrillation (AF)-related pro-inflammatory cytokines at 4 days after surgery. (A) Fold mRNA expression of interleukin (IL)-6, IL-1β, transforming growth factor-β1 (TGF-β1) and IL-17A. (B) Protein expression of IL-17A detected by western blot analysis. (C) Quantitative analysis of IL-17A protein expression. *P<0.05 and **P<0.01 vs. Sham. #P<0.05 and ##P<0.01 vs. IgG2a. Sham, sham-operated rats; SP, rats with sterile pericarditis.

Mentions: To determine the involvement of IL-17A in post-operative AF, we measured the IL-17A levels in the atrial samples following surgery. The mRNA expression of IL-17A began to increase at day 1 following surgery, reached a peak on day 4, and then gradually decreased (Fig. 3A). This result was confirmed by western blot analysis, which revealed an increased expression of IL-17A on day 4 compared with the sham-operated rats (P< 0.05; Fig. 6B). Of note, the time course of IL-17A expression coincided with the probability of AF episodes. When the level of IL-17A reached its peak on day 4, the probability of AF episodes increased to the highest level. Linear correlation analysis of the association between the expression of IL-17A and the probability of AF episodes was performed. The correlation coefficient was 0.95 (Fig. 3B). Our data indicate that IL-17A may contribute to the induction of AF in rats with SP.


Interleukin-17A contributes to the development of post-operative atrial fibrillation by regulating inflammation and fibrosis in rats with sterile pericarditis.

Fu XX, Zhao N, Dong Q, Du LL, Chen XJ, Wu QF, Cheng X, Du YM, Liao YH - Int. J. Mol. Med. (2015)

Expression of atrial fibrillation (AF)-related pro-inflammatory cytokines at 4 days after surgery. (A) Fold mRNA expression of interleukin (IL)-6, IL-1β, transforming growth factor-β1 (TGF-β1) and IL-17A. (B) Protein expression of IL-17A detected by western blot analysis. (C) Quantitative analysis of IL-17A protein expression. *P<0.05 and **P<0.01 vs. Sham. #P<0.05 and ##P<0.01 vs. IgG2a. Sham, sham-operated rats; SP, rats with sterile pericarditis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494571&req=5

f6-ijmm-36-01-0083: Expression of atrial fibrillation (AF)-related pro-inflammatory cytokines at 4 days after surgery. (A) Fold mRNA expression of interleukin (IL)-6, IL-1β, transforming growth factor-β1 (TGF-β1) and IL-17A. (B) Protein expression of IL-17A detected by western blot analysis. (C) Quantitative analysis of IL-17A protein expression. *P<0.05 and **P<0.01 vs. Sham. #P<0.05 and ##P<0.01 vs. IgG2a. Sham, sham-operated rats; SP, rats with sterile pericarditis.
Mentions: To determine the involvement of IL-17A in post-operative AF, we measured the IL-17A levels in the atrial samples following surgery. The mRNA expression of IL-17A began to increase at day 1 following surgery, reached a peak on day 4, and then gradually decreased (Fig. 3A). This result was confirmed by western blot analysis, which revealed an increased expression of IL-17A on day 4 compared with the sham-operated rats (P< 0.05; Fig. 6B). Of note, the time course of IL-17A expression coincided with the probability of AF episodes. When the level of IL-17A reached its peak on day 4, the probability of AF episodes increased to the highest level. Linear correlation analysis of the association between the expression of IL-17A and the probability of AF episodes was performed. The correlation coefficient was 0.95 (Fig. 3B). Our data indicate that IL-17A may contribute to the induction of AF in rats with SP.

Bottom Line: Western blot analysis was applied to quantify the expression of IL-17A.Quantitative PCR was used to detect the mRNA expression of IL-17A, IL-6, IL-1β, transforming growth factor-β1 (TGF-β1), collagen type 1 (Col-1), collagen type 3 (Col-3) and α-smooth muscle actin (α-SMA).Gelatin zymography and reverse gelatin zymography were used to quantify the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs).

View Article: PubMed Central - PubMed

Affiliation: Research Center of Ion Channelopathy, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

ABSTRACT
Post-operative atrial fibrillation (AF) remains a common cause of morbidity. Increasing evidence indicates that inflammation and atrial fibrosis contribute to the pathogenesis of this condition. Interleukin (IL)-17A, a potent pro-inflammatory cytokine, has been implicated in the development of a number of cardiovascular diseases. However, its role in post-operative AF remains unknown. In the present study, sterile pericarditis (SP) was induced in rats by the epicardial application of sterile talc. AF was induced by transesophageal burst pacing. Western blot analysis was applied to quantify the expression of IL-17A. Quantitative PCR was used to detect the mRNA expression of IL-17A, IL-6, IL-1β, transforming growth factor-β1 (TGF-β1), collagen type 1 (Col-1), collagen type 3 (Col-3) and α-smooth muscle actin (α-SMA). Gelatin zymography and reverse gelatin zymography were used to quantify the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Histological analyses were performed to determine the extent of tissue inflammation and fibrosis. The rats with SP presented with a shorter refractoriness, a higher incidence and duration of AF, an enhanced susceptibility to developing AF, increased mRNA levels of AF-related pro-inflammatory cytokines (IL-6, IL-1β and TGF-β1), as well as marked atrial inflammation and fibrosis. The atrial IL-17A levels were elevated and correlated with the probability of developing AF. Treatment with anti-IL-17A monoclonal antibody decreased the levels of atrial IL-17A, prolonged refraction and markedly suppressed the development of AF. Simultaneously, inflammation and fibrosis were alleviated, which was further demonstrated by a decreased expression of AF-related pro-inflammatory cytokines, a downregulation in fibrosis-related mRNA expression (Col-1, Col-3 and α-SMA) and by the decreased activity of MMP-2/9 and TIMPs. Thus, the findings of our study indicate that IL-17A may play a pathogenic role in post-operative AF by inducing inflammation and fibrosis in rats with SP.

No MeSH data available.


Related in: MedlinePlus