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Calpains and cytokines in fibrillating human atria
Andreas Goette1, Marco Arndt, Christoph Röcken
1Division of Cardiology, Department of Internal Medicine, University Hospital Magdeburg, 39120 Magdeburg, Germany. andreas.goette@medizin.uni-magdeburg.de
Insights
Atrial fibrillation (AF) involves calcium overload. This study found increased calpain I activation in AF atria, potentially causing structural changes and dysfunction, while cytokines remained unchanged.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Atrial fibrillation (AF) is linked to intracellular calcium overload.
- Calcium-dependent enzymes, like calpains, may play a role in AF pathophysiology.
- Understanding these mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of calcium-dependent calpains and cytokines in atrial tissue during AF.
- To compare the expression and activity of specific proteins in patients with AF versus sinus rhythm (SR).
Main Methods:
- Atrial tissue samples were obtained from 32 patients (16 with AF, 16 with SR).
- Expression levels of calpain I, calpain II, calpastatin, troponin T (TnT), troponin C (TnC), and various cytokines were measured.
- Calpain enzymatic activity was quantified.
- Myofilament structure was examined using electron microscopy.
Main Results:
- Calpain I expression was significantly increased in AF atria (461% vs. 100%, P < 0.05).
- Total calpain enzymatic activity was more than doubled in AF (35.2 vs. 12.4 units, P < 0.05).
- Troponin T (TnT) levels were reduced by 26% in AF atria, correlating with myofilament disintegration.
Conclusions:
- Permanent AF is associated with activated calpain I in atrial tissue.
- Calpain I activation may contribute to structural remodeling and impaired contractile function in AF.
- No evidence of activated tissue cytokines was found in AF atria.
Abstract:
Atrial fibrillation (AF) is accompanied by intracellular calcium overload. The purpose of this study was to assess the role of calcium-dependent calpains and cytokines during AF. Atrial tissue samples from 32 patients [16 with chronic AF and 16 in sinus rhythm (SR)] undergoing open heart surgery were studied. Atrial expression of calpain I and II, calpastatin, troponin T (TnT), troponin C (TnC), and cytokines [interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, transforming growth factor (TGF)-beta 1, and tumor necrosis factor-alpha] were determined. Expression of calpain I was increased during AF (461 +/- 201% vs. 100 +/- 34%, P < 0.05). Amounts of calpain II and calpastatin were unchanged. Total calpain enzymatic activity was more than doubled during AF (35.2 +/- 17.7 vs. 12.4 +/- 9.2 units, P < 0.05). In contrast to TnC, TnT levels were reduced in fibrillating atria by 26% (P < 0.05), corresponding to the myofilament disintegration seen by electron microscopy. Small amounts of only IL-2 and TGF-beta 1 mRNA and protein were detected regardless of the underlying cardiac rhythm. In conclusion, atria of patients with permanent AF show evidence of calpain I activation that might contribute to structural remodeling and contractile dysfunction, whereas there is no evidence of activation of tissue cytokines.