钙网织蛋白促进心脏瓣膜病患者心房重构

 目的: 明确钙网织蛋白的异常表达与分布能否促进心脏瓣膜病患者心房重构的发生。方法: 从78位进行瓣膜置换手术的患者中获得左右心房的标本。患者被分为窦性节律组、阵发性房颤组和持续性房颤组(房颤持续超过6个月),检测心房组织中钙网织蛋白、整合素α5和转化生长因子β1(TGF-β1)的蛋白表达情况。同时使用免疫共沉淀法测定钙网织蛋白与钙调磷酸酶B及整合素α5的结合情况。结果: 房颤组的钙网织蛋白、整合素α5和TGF-β1的蛋白表达均高于窦性节律组,特别是在二尖瓣疾病患者的左心房中。免疫共沉淀显示钙网织蛋白可以与钙调磷酸酶B和整合素α5结合产生相互作用。整合素α5的表达水平与TGF-β1的表达具有明显相关性,钙网织蛋白表达水平与整合素α5和TGF-β1的表达水平具有明显的相关性。在相同心功能分级情况下,钙网织蛋白的表达水平在持续性房颤组明显高于窦性心律组。结论: 房颤患者心房组织中的钙网织蛋白、整合素α5和TGF-β1表达增高,并与房颤类型有关,这提示钙网织蛋白参与了心脏瓣膜病房颤患者的心房重构。

Over-expressed calreticulin interacts with integrin-α5 and calcineurin system to induce atrial remodeling in patients with atrial fibrillation and valvular disease

AIM: To determine whether calreticulin over-expression contributes to atrial fibrosis in the patients with atrial fibrillation (AF) and valvular heart disease (VHD).METHODS: Right and left atrial specimens were obtained from 78 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR) group, paroxysmal AF (PaAF) group and persistent AF (PeAF, AF lasting >6 months) group. The protein expression of calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) was measured. Immunoprecipitation was also performed to determine whether calreticulin interacted with either calcineurin B or integrin-α5. RESULTS: The protein expression of calreticulin, integrin-α5 and TGF-β1 was increased in AF groups, especially in the left atrium of the patients with mitral valve disease as compared with SR group. Calreticulin interacted with both calcineurin B and integrin-α5. The expression level of integrin-α5 was significantly correlated with the expression level of TGF-β1, while the expression level of calreticulin was correlated with that of integrin-α5 and TGF-β1. Under similar classification of the cardiac function, the expression level of calreticulin in PeAF group was higher than that in SR group. CONCLUSION: The expression of calreticulin, integrin-α5, and TGF-β1 is increased in the atrial tissues of the AF patients and is related to the AF type, suggesting that calreticulin is involved in atrial remodeling in AF and VHD patients.