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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

Analysis of the inducibility of atrial fibrillation (AF) in sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A) Typical transesophageal and surface electrogram recordings following the induction of AF. (B) Quantification of the number of AF episodes. (C) Total duration of AF episodes. (D) Probability of the development of AF, defined as inducible episodes divided by the number of total testing maneuvers applied. *P<0.05 and **P<0.01 vs. Sham.
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f1-ijmm-36-01-0083: Analysis of the inducibility of atrial fibrillation (AF) in sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A) Typical transesophageal and surface electrogram recordings following the induction of AF. (B) Quantification of the number of AF episodes. (C) Total duration of AF episodes. (D) Probability of the development of AF, defined as inducible episodes divided by the number of total testing maneuvers applied. *P<0.05 and **P<0.01 vs. Sham.

Mentions: The basic cardiac electrophysiology data are presented in Table II. Both the ARPs and AVNRPs measured were significantly shorter in the rats with SP at the S1S1 CLs of 120, 110 and 100 msec with a 10 msec stepwise S1S2 reduction starting 10 msec after S1S1 (P<0.05). However, no significant differences were observed in the parameters examined. AF was repeatedly induced by burst pacing as described in the Materials and methods. Typical transesophageal and surface electrogram recordings following the induction of AF are illustrated in Fig. 1A. The rats with SP showed a higher susceptibility to the development of AF compared to the sham-operated rats, with a higher incidence (Fig. 1B) and duration of AF episodes (Fig. 1C), as well as an increased probability of developing AF (Fig. 1D).


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)

Analysis of the inducibility of atrial fibrillation (AF) in sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A) Typical transesophageal and surface electrogram recordings following the induction of AF. (B) Quantification of the number of AF episodes. (C) Total duration of AF episodes. (D) Probability of the development of AF, defined as inducible episodes divided by the number of total testing maneuvers applied. *P<0.05 and **P<0.01 vs. Sham.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-ijmm-36-01-0083: Analysis of the inducibility of atrial fibrillation (AF) in sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A) Typical transesophageal and surface electrogram recordings following the induction of AF. (B) Quantification of the number of AF episodes. (C) Total duration of AF episodes. (D) Probability of the development of AF, defined as inducible episodes divided by the number of total testing maneuvers applied. *P<0.05 and **P<0.01 vs. Sham.
Mentions: The basic cardiac electrophysiology data are presented in Table II. Both the ARPs and AVNRPs measured were significantly shorter in the rats with SP at the S1S1 CLs of 120, 110 and 100 msec with a 10 msec stepwise S1S2 reduction starting 10 msec after S1S1 (P<0.05). However, no significant differences were observed in the parameters examined. AF was repeatedly induced by burst pacing as described in the Materials and methods. Typical transesophageal and surface electrogram recordings following the induction of AF are illustrated in Fig. 1A. The rats with SP showed a higher susceptibility to the development of AF compared to the sham-operated rats, with a higher incidence (Fig. 1B) and duration of AF episodes (Fig. 1C), as well as an increased probability of developing AF (Fig. 1D).

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