■特发性扩张型心肌病(DCM)与细胞骨架蛋白异常有关,线粒体ATP转运蛋白,微脉管系统,和纤维化。间充质干细胞(MSCs)可以改善受损的线粒体和结构蛋白,以及纤维化,通过细胞因子的旁分泌作用。本研究旨在研究脂肪组织来源的MSCs(ADSCs)移植是否通过调节腺嘌呤核苷酸转位酶1(ANT-1)的表达来逆转DCM样仓鼠受损心肌的组织学和功能异常。
■出生后18周,将ADSC植入δ-肌聚糖(SG)缺陷仓鼠的心脏表面上或进行假手术。
■在ADSC治疗的动物中维持左心室射血分数和收缩末期直径4周,这些动物的心肌细胞中ATP浓度显著升高,ANT-1表达也显著上调。细胞外基质和心肌细胞骨架蛋白的表达,如胶原蛋白,SG,和α-营养不良聚糖,组之间没有差异。然而,肌球蛋白和Smad4表达显着改善,心肌细胞肥大,ADSC治疗组出现毛细血管密度。
■我们证明了ADSCs可能通过提高ATP浓度来维持DCM仓鼠模型的心功能,以及线粒体转运蛋白和肌球蛋白的表达,表明了他们治疗DCM的潜力。
UNASSIGNED: Idiopathic dilated cardiomyopathy (DCM) is associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. Mesenchymal stem cells (MSCs) can ameliorate distressed mitochondrial and structural proteins, as well as fibrosis, via the paracrine effect of cytokines. This study aimed to investigate whether the transplantation of adipose tissue-derived MSCs (ADSCs) reverses histological and functional abnormalities in the distressed myocardium of DCM-like hamsters by modulating the expression of adenine nucleotide translocase 1 (ANT-1).
UNASSIGNED: Eighteen weeks after birth, ADSCs were implanted onto the cardiac surface of δ-sarcoglycan (SG)-deficient hamsters or sham surgery was performed.
UNASSIGNED: Left ventricular ejection fraction and end-systolic diameter were maintained in ADSC-treated animals for four weeks, ATP concentration was considerably elevated in the cardiomyocytes of these animals, and ANT-1 expression was significantly upregulated as well. The expression of extracellular matrix and myocardial cytoskeletal proteins, such as collagen, SG, and α-dystroglycan, did not differ between groups. However, significant improvements in myosin and Smad4 expression, cardiomyocyte hypertrophy, and capillary density occurred in the ADSC-treated group.
UNASSIGNED: We demonstrated that ADSCs might maintain cardiac function in the DCM hamster model by enhancing ATP concentration, as well as mitochondrial transporter and myosin expression, indicating their potential for DCM treatment.