Masuelli Laura, Trono Paola, Marzocchella Laura, Mrozek Marie-Agnes, Palumbo Camilla, Minieri Marilena, Carotenuto Felicia, Fiaccavento Roberta, Nardi Alessandra, Galvano Fabio, Di Nardo Paolo, Modesti Andrea, Bei Roberto
Department of Experimental Medicine, University of Rome Sapienza, Rome, Italy.
Int J Mol Med. 2008 Jan;21(1):41-8.
Cardiomyocyte intercalated disks of delta-sarcoglycan-deficient cardiomyopathic hamsters (CMPHs) exhibit a pathological accumulation of the N-cadherin/catenin complex. CMPHs fed with an alpha-linolenic acid (ALA)-enriched diet (CMPH/FS) display an extended longevity compared to those fed with a standard diet (CMPH/PT) owing to, among others, the amelioration of both cardiac tissue structure and myocardial function. The present investigation was aimed at evaluating whether and to what extent the ALA-enriched diet affects the remodeling of CMPH cardiomyocyte intercalated disks and the expression of molecules, including N-cadherin, catenins and connexin 43 (CX43), involved in their organization. Western blot and immunohistochemical analysis demonstrated that the expression of N-cadherin, alpha- and beta-catenin is significantly reduced in cardiomyocyte intercalated disks of CMPH/FS vs. CMPH/PT and is lowered to levels similar to those found in healthy hamsters (GSH/PT), as well as transmission electron microscopy indicated that the cardiomyocyte intercalated disk ultrastructure is also re-established in CMPH/FS. In addition, the delocalization of CX43 as well as the presence of gap junctions were detectable at the lateral plasmamembrane of CMPH/FS cardiomyocytes, while the expression of myocardial CX43 was markedly reduced in both CMPH/PT and CMPH/FS, as compared to GSH/PT. Collectively, the present results demonstrate a substantial effect of an ALA-enriched diet on cardiomyocyte intercalated disk structure and molecular composition and further supports the beneficial effects of omega-3 polyunsaturated fatty acids in the prevention of potentially dangerous arrhythmias in cardiac diseases.
δ-肌聚糖缺乏型心肌病仓鼠(CMPH)的心肌细胞闰盘表现出N-钙黏蛋白/连环蛋白复合体的病理性积聚。与喂食标准饮食的仓鼠(CMPH/PT)相比,喂食富含α-亚麻酸(ALA)饮食的CMPH(CMPH/FS)寿命延长,这尤其归因于心脏组织结构和心肌功能的改善。本研究旨在评估富含ALA的饮食是否以及在多大程度上影响CMPH心肌细胞闰盘的重塑以及参与其组织的分子表达,包括N-钙黏蛋白、连环蛋白和连接蛋白43(CX43)。蛋白质免疫印迹和免疫组织化学分析表明,与CMPH/PT相比,CMPH/FS心肌细胞闰盘中N-钙黏蛋白、α-连环蛋白和β-连环蛋白的表达显著降低,并降至与健康仓鼠(GSH/PT)中发现的水平相似,同时透射电子显微镜显示CMPH/FS中心肌细胞闰盘超微结构也得以重建。此外,在CMPH/FS心肌细胞的侧质膜上可检测到CX43的错位以及间隙连接的存在,而与GSH/PT相比,CMPH/PT和CMPH/FS中心肌CX43的表达均显著降低。总体而言,目前的结果表明富含ALA的饮食对心肌细胞闰盘结构和分子组成有显著影响,并进一步支持了ω-3多不饱和脂肪酸在预防心脏疾病中潜在危险心律失常方面的有益作用。