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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

Assessment of inflammation and fibrosis in the sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A–C) Relative mRNA level of atrial fibrillation (AF)-related pro-inflammatory cytokines: (A) interleukin (IL)-6, (B) IL-1β and (C) transforming growth factor-β1 (TGF-β1) in the atril samples during post-operative days 0–7. (D and E) Representative histological sections stained with (D) hematoxylin and eosin (H&E) and (E) Masson’s trichrome at 4 days after surgery. Original magnification, x400. The rats with SP presented with a significant number of infiltrating inflammatory cells and extensice fibrosis.
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f2-ijmm-36-01-0083: Assessment of inflammation and fibrosis in the sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A–C) Relative mRNA level of atrial fibrillation (AF)-related pro-inflammatory cytokines: (A) interleukin (IL)-6, (B) IL-1β and (C) transforming growth factor-β1 (TGF-β1) in the atril samples during post-operative days 0–7. (D and E) Representative histological sections stained with (D) hematoxylin and eosin (H&E) and (E) Masson’s trichrome at 4 days after surgery. Original magnification, x400. The rats with SP presented with a significant number of infiltrating inflammatory cells and extensice fibrosis.

Mentions: An increase in the expression of pro-inflammatory cytokines has been reported to be associated with post-operative AF (24,25) and in animal models of SP as well (26,27). Thus, in this study, we examined cytokine expression in the atria of the rats on post-operative days 0-7. The mRNA levels of IL-6 and IL-1β increased significantly as early as 1 day following pericardiotomy, reached peak levels on day 2 and then began to decrease, confirming a previous observation (27) (Fig. 2A and B). By contrast, the TGF-β1 mRNA level increased progressively (Fig. 2C).


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)

Assessment of inflammation and fibrosis in the sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A–C) Relative mRNA level of atrial fibrillation (AF)-related pro-inflammatory cytokines: (A) interleukin (IL)-6, (B) IL-1β and (C) transforming growth factor-β1 (TGF-β1) in the atril samples during post-operative days 0–7. (D and E) Representative histological sections stained with (D) hematoxylin and eosin (H&E) and (E) Masson’s trichrome at 4 days after surgery. Original magnification, x400. The rats with SP presented with a significant number of infiltrating inflammatory cells and extensice fibrosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ijmm-36-01-0083: Assessment of inflammation and fibrosis in the sham-operated rats (Sham) and rats with sterile pericarditis (SP). (A–C) Relative mRNA level of atrial fibrillation (AF)-related pro-inflammatory cytokines: (A) interleukin (IL)-6, (B) IL-1β and (C) transforming growth factor-β1 (TGF-β1) in the atril samples during post-operative days 0–7. (D and E) Representative histological sections stained with (D) hematoxylin and eosin (H&E) and (E) Masson’s trichrome at 4 days after surgery. Original magnification, x400. The rats with SP presented with a significant number of infiltrating inflammatory cells and extensice fibrosis.
Mentions: An increase in the expression of pro-inflammatory cytokines has been reported to be associated with post-operative AF (24,25) and in animal models of SP as well (26,27). Thus, in this study, we examined cytokine expression in the atria of the rats on post-operative days 0-7. The mRNA levels of IL-6 and IL-1β increased significantly as early as 1 day following pericardiotomy, reached peak levels on day 2 and then began to decrease, confirming a previous observation (27) (Fig. 2A and B). By contrast, the TGF-β1 mRNA level increased progressively (Fig. 2C).

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