Relationship Between The Protein Expression Of Calpain-2 And Calcineurin And Valvular Atrial Fibrillation

BackgroundAtrial fibrillation (AF) is a common complication of valvular heart disease (VHD). In addition to the reduction of cardiac function by 20-30%, its most serious consequence is cerebral embolism. AF can be divided into valvular atrial fibrillation (VAF) and non-valvular atrial fibrillation (NVAF) according to the pathogenesis. Several studies showed that the risk of cerebral embolism in patients with NVAF is 5-7 folds than that in patients without AF, and the risk in patients with VAF is 17 times than that in sinus rhythm patients. Therefore, it is of great importance for us to study the mechanism of VHD in order to prevent the occurrence of cerebral embolism. It is well known that the calcineurin (CaN) signal pathway is associated with the occurrence of AF. However, it is unclear weather this pathway is involved in VAF. Genetic studies demonstrated that the expression of CaN mRNA was increased in both peripheral lymphocytes and myocardial tissue of patients with VAF than those in VHD patients without AF. Calpain-2, a cysteine protease, plays an important role in the regulation of CaN activity. The autoinhibitory domain of full-length CaN (60KD) can be cleaved by activated calpain-2, resulting in a 45 KD truncated active form. The expression of Calpain-2 mRNA was similar to that of CaN in cardiac tissues. Taken together, these findings suggest that CaN signal pathway is involved in the occurrence of VAF as well. Since there is no report about the association of protein expression levels of CaN and calpain-2 with VHD, therefore we conducted this study.ObjectiveThe aim of this study was to investigate the relationship between the protein expression of calpain-2 and calcineurin (CaN) and atrial fibrillation (AF) in patient with valvular heart disease (VHD).MethodsA total of 40 patients who underwent valve replacement surgery were divided into two groups according to their heart rhythm:sinus rhythm (SR) group (n=17) and AF group (n=23). The protein expression levels for calpain-2 and the a-isoform of CaN catalytic subunit (CnA) in the right atrial appendages were measured by Western Blot, with β-actin as an internal reference.Results1. Clinical data. The heart rate of patients with AF is faster than that of patients with SR (P<0.05). There is no difference between patients with AF and those with SR in age, gender, body mass index (BMI)、smoking history、drinking history、 blood pressure and hemoglobin (Table 4).2. Medicines. The ratio of patients with AF who take digoxin is higher than that of patients with SR (P<0.05). There is no difference in other drugs between patients with AF and those with SR (P>0.05) (Table 5).3. Echocardiography. In comparison with the data in patients with SR, the diameter of left atrium in patients with AF is larger (P<0.05) (Table 6).4. Western blot. The protein levels of the full-length (60KD) and the 45KD-fragment of CnAα were increased in the AF group in comparison with those in the SR group (0.76±0.37 vs 1.25±0.51 and 0.76±0.25 vs 1.08±0.37, respectively; all P<0.05). Similarly, the protein expression of calpain-2 was increased in the AF group in comparison with those in the SR group (0.51±0.19 vs 0.82±0.44, P<0.05) (Figurel).ConclusionCalpain-2-CaN signal pathway might be involved in the pathogenesis of VAF.