2.High mobility group box 1 protein: possible pathogenic link to atrial fibrillation.
Xiao-Rong HU ; Xiao-Hong WANG ; Hua-Fen LIU ; Wen-Jie ZHOU ; Hong JIANG
Chinese Medical Journal 2012;125(13):2346-2348
Atrial fibrillation (AF) is the most common sustained dysrhythmia in clinical practice. The bulk of evidence suggests that inflammatory processes, oxidative stress and matrix metalloproteinase are associated with development of AF. However, these agents may be involved in high mobility group box 1 protein (HMGB1). We hypothesized that HMGB1 may be a possible pathogenic link to AF. A growing body of evidence supports these hypotheses. First, the level of serum HMGB1 is significantly increased in patients with AF including paroxysmal and persistent AF. Second, HMGB1 has been identified as a new pro-inflammatory cytokine in cardiovascular diseases, along with tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein, and there is cross-talk between HMGB1 and inflammatory cytokines. Third, oxidative stress is involved in the release of the pro-inflammatory cytokine, HMGB1, indicating there is cross-talk between oxidative stress and inflammation, and oxidative stress may reinforce the effect of inflammation on the pathogenesis of AF and inflammation may play a more important role in the pathogenesis of AF. Fourth, HMGB1 can promote matrix metalloproteinase-9 upregulation and activation. Fifth, HMGB1 receptors (receptor for advanced glycation end products, Toll-like receptor-2,4) may mediate the atrial structural remodeling or be up-regulated in patients with non-valvular AF. These results suggest that HMGB1 may participate in the pathogenesis of AF and provide a potential target for pharmacological interruption of AF.
Atrial Fibrillation
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metabolism
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HMGB1 Protein
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metabolism
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Humans
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Metalloendopeptidases
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metabolism
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Oxidative Stress
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physiology
3.Study on expression of mineralocorticoid receptor in human atria during atrial fibrillation.
De-an PEI ; Li LI ; Zhi-yun XU ; Liang-jian ZOU ; Bao-ren ZHANG ; Sheng-dong HUANG ; Jia-hua HAO ; Zhi-nong WANG ; Fang-lin LU
Chinese Journal of Cardiology 2007;35(2):114-118
OBJECTIVETo investigate the mRNA and protein expression of mineralocorticoid receptor (MR) in patients with atrial fibrillation.
METHODSTwenty-five patients with rheumatic heart valve disease, 12 in sinus rhythm and 13 in chronic atrial fibrillation (>or= 6 months), underwent transthoracic echocardiography and right and left atrial lateral wall tissue samples were obtained from these patients during mitral/aortic valve replacement operation. Realtime quantitative PCR and Western blot were used to determine the mRNA and protein expression of MR in atria specimens. The distribution of MR in human atria was analyzed by specific immunohistochemical staining.
RESULTSThe left atrial diameters increased markedly in atrial fibrillation group compared with that in sinus rhythm group (P<0.01). And the results showed that the level of mRNA and protein of MR were increased significantly in atrial fibrillation group compared with those in sinus rhythm group (P<0.01 or 0.05), whereas the expression of mRNA and protein of MR were found to be no difference between left atria and right atria both in fibrillation and sinus groups (all P>0.05). The special immunohistochemical staining demonstrated that MR was abundant in the human atrial myocardium and MRs were located mainly in the cytoplasm of atrial cells, which were more evident in atrial fibrillation group than those in sinus rhythm group.
CONCLUSIONThese findings suggested that MRs were upregulated in atrial fibrillation and aldosterone antagonists may be effective in treating atrial fibrillation.
Adult ; Atrial Fibrillation ; metabolism ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; RNA, Messenger ; genetics ; Receptors, Mineralocorticoid ; metabolism
4.Relationships of High-sensitive C-reactive Protein and P-wave Dispersion in Lone Atrial Fibrillation.
Li-Hui ZHENG ; Yan YAO ; Ling-Min WU ; Kui-Jun ZHANG ; Shu ZHANG
Chinese Medical Journal 2015;128(11):1450-1454
BACKGROUNDCurrent evidence links atrial fibrillation (AF) to the inflammation. Inflammatory indexes such as high-sensitive C-reactive protein (hs-CRP) have been related to the development and persistence of AF. However, the role of inflammation in the atrial electrophysiological remodeling indexed by P-wave dispersion (P d ) remains unclear.
METHODSThe study consisted of 71 patients with lone paroxysmal AF (AF group) and 71 age- and gender-matched controls of paroxysmal supraventricular tachycardia without history of AF (control group). Electrocardiography, P d , hs-CRP, and other clinical characteristics were compared between the two groups.
RESULTSThere was no significant difference between the two groups regarding age, gender, hyperlipidemia, etc. Compared to controls, left atrial diameter (44 ± 7 vs 39 ± 7 mm), P d (49 ± 13 vs 26 ± 8 ms), and hs-CRP (2.17 [1.46-2.89] vs 1.12 [0.74-1.41] mg/L) were increased (P < 0.05), respectively. Linear regression identified hs-CRP as an independent correlation of P d level both in the total population and the AF group (r = 0.464 and 0.313; P < 0.001, respectively). Multiple logistic regression revealed hs-CRP as an independent determinant of AF (odds ratio [OR] =15.430, 95% confidence interval: 6.031-39.476: P <0.001). Further adjusted for P d , both P d and hs-CRP were independent predictors for AF, but the OR for hs-CRP in predicting AF has been attenuated from 15.430 to 6.246.
CONCLUSIONSIn lone AF, P d and plasma hs-CRP concentration are inter-associated and related to AF. The interaction between hs-CRP and AF may be mediated by P d , suggesting an important role of inflammation in the atrial electrophysiological remodeling predisposing to AF.
Aged ; Atrial Fibrillation ; metabolism ; physiopathology ; C-Reactive Protein ; metabolism ; Female ; Humans ; Male ; Middle Aged
5.Electrical remodeling in human atrial fibrillation.
Chinese Medical Journal 2013;126(12):2380-2383
Animals
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Atrial Fibrillation
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physiopathology
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Atrial Remodeling
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physiology
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Calcium
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metabolism
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Humans
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Inflammation
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etiology
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Ion Channels
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physiology
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MicroRNAs
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physiology
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Oxidative Stress
6.Calpain I inhibition prevents pacing-induced structural remodeling for atrial fibrillation in canine.
Wei-min LI ; Hong-jie XUE ; Yue LI ; Li ZHANG ; Yong-tai GONG ; Li SHENG ; Shan CHU
Chinese Journal of Cardiology 2007;35(2):132-136
OBJECTIVETo study the relation of the structural remodeling processes and activation of calpain I.
METHODSFifteen dogs were randomly divided into three groups. The dogs in pacing group (n=5) and inhibitor group (n=5) were subjected to 3 weeks of rapid atrial pacing at 600 beats/min, control dogs (n=5) were in sham-operated group. The dogs in inhibitor group were administered intravenous N-Acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, and in pacing group and sham-operated group were administered intravenous DMSO. The activity of calpain I was measured by hydrolyzing Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. The ultrastructure of atrium was examined by light and electron microscopy. TnT expression was assessed by Western blot. Echocardiography examination was performed in all the three groups.
RESULTSCalpain I activity was significantly increased in pacing group (2.3-fold, P<0.01), and decreased in inhibitor group (1.1-fold, P>0.05), compared to sham-operated group respectively. The percentages of myolysis were (76.7 +/- 5.9)% and (20.8 +/- 8.1)% in pacing group and inhibitor group respectively (P<0.01). TnT expression decreased in the rapid pacing-induced persistent atrial fibrillation, and these effects were inhibited by calpain I inhibitor ALLM. The area and volume of left atrium tended to increase after 3 weeks ALLM treatment in inhibitor group, but the change was not as prominent as in pacing group (P<0.05).
CONCLUSIONSALLM can decrease calpain I activity, and prevent canine atrial cardiomyocyte structural remodeling during atrial fibrillation. This study provided a capacity of atrial cardiomyocyte protection.
Animals ; Atrial Fibrillation ; metabolism ; physiopathology ; Atrial Function, Left ; Calpain ; antagonists & inhibitors ; metabolism ; Cardiac Pacing, Artificial ; Disease Models, Animal ; Dogs ; Heart Atria ; ultrastructure ; Myocardium ; metabolism ; Troponin T ; metabolism
7.Expressions of L-type calcium channel and potassium channel Kv4.3 in rapid paced primary cultured atrial myocytes.
Wei CHENG ; Ying-bin XIAO ; Xue-feng WANG ; Lin CHEN ; Qian-jin ZHONG
Chinese Journal of Cardiology 2006;34(4):312-315
OBJECTIVETo study the expressions of L-type calcium channel alpha1c and potassium channel Kv4.3 at early stages of atrial fibrillation in a rapid paced primary cultured atrial myocyte model.
METHODSPrimary rat atrial myocytes were cultured and a rapid paced cell model was established. The atrial cells were divided into five groups with pacing durations within 0 and 24 h. Reverse transcription-polymerase chain reaction and Western blot were applied to detect the messenger ribonucleic acid (mRNA) and proteins of L-type calcium channel alpha1c and potassium channel Kv4.3, respectively.
RESULTSmRNA expression of L-type calcium channel alpha1c reduced after 6 h of rapid pacing and continued to decline as the pacing process. The decrease of L-type calcium channel alpha1c protein was paralleled with mRNA expression and reached the lowest levels at 24 h. Similarly, changes of potassium channel Kv4.3 protein and mRNA were paralleled. Kv4.3 mRNA was not altered within the first 6 h. It was reduced after 12 h. However, longer pacing periods did not further decrease mRNA and protein expression levels of potassium channel Kv4.3.
CONCLUSIONSExpressions of L-type calcium channel alpha1c and potassium channel Kv4.3 were both reduced at different levels in early phase of rapid pacing atrial myocytes. It implicates the occurrence of ion channel remodeling of atrial myocytes, which may serve as molecular mechanism of electrical remodeling in the development of atrial fibrillation.
Animals ; Atrial Fibrillation ; metabolism ; physiopathology ; Calcium Channels, L-Type ; metabolism ; Cardiac Pacing, Artificial ; Cells, Cultured ; Myocytes, Cardiac ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Shal Potassium Channels ; metabolism
8.Calpain-I, calpastatin, caspase-3 and apoptosis in the human left atrium in rheumatic atrial fibrillation.
Yun-qing CHEN ; Lin WANG ; Xi SU ; Liang TAO ; Xu-fa CHEN
Chinese Journal of Cardiology 2006;34(4):303-307
OBJECTIVEThe aim of the present study was to detect the expression of calpain-I, calpastatin, caspase-3 and apoptosis in the left atria of patients with rheumatic heart disease (RHD), and to find the association of these factors. Also, it was intended to investigate the effect of the above factors on the mechanism of atrial fibrillation (AF).
METHODS43 patients with RHD undergoing valve-replacement were included, 15 patients with regular sinus rhythm (Group RSR), 8 patients with paroxysmal AF (Group AF1) and 20 patients with permanent AF (Group AF2). Western blot was used to examine the content of calpain-I, caspase-3 and calpastatin. The apoptosis index (AI) was measured by TUNEL.
RESULTS(1) Expression of calpain-I in group AF2 was increased to (344.0 +/- 101.9)%, and caspase-3 was increased to (394.0 +/- 99.4)% compared to group RSR (P < 0.01, respectively). Amount of calpastatin was reduced to (27.0 +/- 12.8)% (P < 0.01). The expressions of these proteins were unchanged in group AF1. (2) AI in group AF2 was higher than that in groups RSR and AF1 (P < 0.01). (3) In group AF2, the levels of calpain-I, caspase-3 and AI were positively relative to left atrial dimension and AF duration, P < 0.05 - 0.01, respectively, whereas calpastatin was negatively correlated with left atrial dimension and AF duration (P = 0.007 and P = 0.001, respectively). (4) The protein content of calpain-I was positively related with that of caspase-3 and AI (P < 0.01, respectively), and the content of calpastatin was negatively related with that of calpain-I and caspase-3 (P < 0.01, respectively).
CONCLUSIONSApoptosis of atrial cell increased in left atria and the protein contents of calpain-I, caspase-3 and calpastatin significantly altered during AF in humans with RHD. The observed interactions suggest that these factors compose a system to cause the structural remodeling and dysfunction of atria. The course may play a key role in promoting the onset and maintenance of AF.
Adult ; Apoptosis ; Atrial Fibrillation ; etiology ; metabolism ; Atrial Function ; Calcium-Binding Proteins ; metabolism ; Calpain ; metabolism ; Caspase 3 ; metabolism ; Female ; Heart Atria ; metabolism ; Humans ; Male ; Middle Aged ; Myocytes, Cardiac ; metabolism ; Rheumatic Heart Disease ; complications ; metabolism
9.Changes of interleukin-1beta and tumor necrosis factor-alpha of right atrial appendages in patients with rheumatic valvular disease complicated with chronic atrial fibrillation.
Chang-hua WANG ; Da-yi HU ; Chu-zhong TANG ; Ming-ying WU ; Yun-qing MEI ; Jian-gang ZHAO ; Hong-wei QI
Chinese Journal of Cardiology 2005;33(6):522-525
OBJECTIVETo investigate whether atrial expression of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) of right atrial appendages are altered in patients with rheumatic valvular disease during chronic atrial fibrillation.
METHODSA total of 48 patients with rheumatic heart disease were included. 27 patients had no history of atrial fibrillation, 21 patients had atrial fibrillation. Atrial tissue was obtained from the right atrial appendage during open heart surgery. The protein expression of IL-1beta and TNF-alpha was detected by immunohistochemistry method. The fibrosis of right atrial appendage was detected by Masson staining.
RESULTSThe fibrosis of right atrial appendage was significantly increased in patients with chronic atrial fibrillation. The protein expression of IL-1beta and TNF-alpha were significantly increased in patients with chronic atrial fibrillation.
CONCLUSIONSThe protein expression of IL-1beta and TNF-alpha were significantly increased in patients with rheumatic valvular disease during chronic atrial fibrillation. Inflammation may be one of the mechanisms for the development and persistence of atrial fibrillation.
Adult ; Aged ; Atrial Fibrillation ; complications ; metabolism ; Female ; Humans ; Interleukin-1beta ; metabolism ; Male ; Middle Aged ; Rheumatic Heart Disease ; complications ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism
10.Effects of intracellular calcium alteration on SK currents in atrial cardiomyocytes from patients with atrial fibrillation.
Hua WANG ; Tao LI ; Li ZHANG ; Yan YANG ; Xiao-Rong ZENG
Chinese Journal of Applied Physiology 2014;30(4):296-305
OBJECTIVESK channels are existed in hearts of mouse, rat, and human. Biochemical evidence indicates that SK2 channels are expressed more in atrial than in ventricular tissue. SK channels are highly sensitive to the calcium concentration of the pipette solution. In the present study, performed whole-cell patch clamp was used to detect the calcium sensitivity of small conductance Ca(2+)-activated K+ channels (SK) currents between sinus ryhthm (SR) and auricular fibrillation (AF).
METHODSThe patients who accepted cardiopulmonary bypass were divided into two groups: 21 patients with SR and 8 patients with AF. The enzymatic dissociation method was improved according to the previous research by our lab. The performed whole cell patch-clamp technique was used to record SK2 currents in both SR and AF groups at room temperature.
RESULTSThe SK2 current density was (-2.92 +/- 0.35) pA/pF in SR group (n = 6) vs (-6.83 +/- 0.19) pA/pF in AF group at -130 mV (n = 3, P < 0.05). In SR group, the SK2 current densities in calcium concentration of the pipette solution are (-1.43 +/- 0.33) pA/pF (n = 7), (-2.92 +/- 0.35) pA/pF (n = 6), (-10.11 +/- 2.15) pA/pF (n = 8, P < 0.05); In AF group, the SK2 current densities are (-2.17 +/- 0.40) pA/pF (n = 4), (-6.83 +/- 0.19) pA/pF (n = 3), (-14.47 +/- 2.89 pA/pF) (n = 4, P < 0.05).
CONCLUSIONThe SK2 currents recorded in this experiment are voltage-independent, inwardly rectifying and apamin-sensitive. When the calcium concentration of the pipette solution is 5 x 10(-7) mol/L, SK2 current density in AF group are significantly larger than those in SR group. It suggests that SK currents involve the cardiomyocytes electric remodeling in AF. In AF group, the SK2 currents are more sensitive to free calcium ion. It shows that the increased sensitivity of SK2 currents to the calcium contribute to the occurrence and maintenance of AF.
Atrial Fibrillation ; metabolism ; physiopathology ; Calcium ; metabolism ; Cells, Cultured ; Heart Atria ; metabolism ; Humans ; Membrane Potentials ; physiology ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; physiology