calpastatin and Atrial-Fibrillation

Changes in connexins and calpains of the myocardial sleeve of the pulmonary vein and the left atrium were investigated in chronic atrial fibrillation (AF) animal models.. There are no reports of changes in the calpain system and connexins in the pulmonary vein where AF is initiated.. An AF animal model was prepared by rapid pacing of the right atrium for 8 weeks. Histological changes of pulmonary veins were analyzed by Masson trichrome staining, and mRNA as well as protein expression of connexins and calpains were measured by real-time fluorescence quantitative PCR and Western blotting.. In AF dogs, the fibrous collagen reticulum surrounding individual myocardial cells was reduced or disrupted. In the myocardial sleeve of the AF dogs, Cx40 protein expression was significantly downregulated compared to the control group (60.78 +/- 10.91 vs. 88.31 +/- 14.73, p < 0.05), but calpain 1 was significantly upregulated (94.00 +/- 7.24 vs. 81.77 +/- 5.82, p < 0.05), and they were negatively correlated (r = -0.66, p < 0.05). Cx40 protein expression was significantly lower in the myocardial sleeve tissue than in the left atrium in the AF dogs (60.78 +/- 10.91 vs. 91.38 +/- 17.16, p < 0.05).. Varied gap junctional remodeling around the pulmonary vein may be one of the underlying mechanisms for pulmonary vein-left atrial reentry. During AF, the calpain system of the myocardial sleeve tissue is activated and may hydrolyze Cx40 protein, which is a possible important molecular mechanism for gap junctional remodeling that merits further investigation.

Topics: Animals; Atrial Fibrillation; Calcium-Binding Proteins; Calpain; Connexin 43; Connexins; Disease Models, Animal; Dogs; Female; Gap Junction alpha-5 Protein; Gap Junctions; Heart Atria; Male; Pacemaker, Artificial; Pulmonary Veins; RNA, Messenger

The 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).. 43 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.. (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).. Apoptosis 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.

Topics: Adult; Apoptosis; Atrial Fibrillation; Atrial Function; Calcium-Binding Proteins; Calpain; Caspase 3; Female; Heart Atria; Humans; Male; Middle Aged; Myocytes, Cardiac; Rheumatic Heart Disease

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.

Topics: Actin Cytoskeleton; Adult; Aged; Atrial Appendage; Atrial Fibrillation; Blotting, Western; Calcium-Binding Proteins; Calpain; Cytokines; Female; Humans; In Vitro Techniques; Interleukin-2; Male; Middle Aged; Myocardium; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1