Laboratorio de Señalización Celular y Nanobiología, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Plataforma de Microscopía de Fuerza Atómica, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay.
Am J Physiol Cell Physiol. 2024 Nov 1;327(5):C1263-C1273. doi: 10.1152/ajpcell.00273.2024. Epub 2024 Oct 7.
Several studies have demonstrated that diabetes mellitus can increase the risk of cardiovascular disease and remains the principal cause of death in these patients. Costameres connect the sarcolemma with the cytoskeleton and extracellular matrix, facilitating the transmission of mechanical forces and cell signaling. They are related to cardiac physiology because individual cardiac cells are connected by intercalated discs that synchronize muscle contraction. Diabetes impacts the nanomechanical properties of cardiomyocytes, resulting in increased cellular and left ventricular stiffness, as evidenced in clinical studies of these patients. The question of whether costameric proteins are affected by diabetes in the heart has not been studied. This work analyzes whether type 1 diabetes mellitus (T1DM) modifies the costameric proteins and coincidentally changes the cellular mechanics in the same cardiomyocytes. The samples were analyzed by immunotechniques using laser confocal microscopy. Significant statistical differences were found in the spatial arrangement of the costameric proteins. However, these differences are not due to their expression. Atomic force microscopy was used to compare intrinsic cellular stiffness between diabetic and normal cardiomyocytes and obtain the first elasticity map sections of diabetic living cardiomyocytes. Data obtained demonstrated that diabetic cardiomyocytes had higher stiffness than control. The present work shows experimental evidence that intracellular changes related to cell-cell and cell-extracellular matrix communication occur, which could be related to cardiac pathogenic mechanisms. These changes could contribute to alterations in the mechanical and electrical properties of cardiomyocytes and, consequently, to diabetic cardiomyopathy. The structural organization of cardiomyocyte proteins is critical for their efficient functioning as a contractile unit in the heart. This work shows that diabetes mellitus induces significant changes in the spatial organization of costamere proteins, tubules, and intercalated discs. We obtained the first elasticity map sections of living diabetic cardiomyocytes. The results show statistical differences in the map sections of diabetic and control cardiomyocytes, with diabetic cardiomyocytes being stiffer than normal ones.
多项研究表明，糖尿病可增加心血管疾病风险，并且仍然是此类患者的主要死亡原因。连接肌膜与细胞骨架和细胞外基质的结构称为连接蛋白，有助于机械力和细胞信号的传递。连接蛋白与心脏生理学有关，因为单个心肌细胞通过闰盘连接，闰盘使肌肉收缩同步。糖尿病影响心肌细胞的纳米力学特性，导致细胞和左心室僵硬度增加，这些在这些患者的临床研究中得到证实。连接蛋白是否受心脏中糖尿病的影响尚未得到研究。本工作分析了 1 型糖尿病（T1DM）是否会改变连接蛋白，并且巧合地改变同一心肌细胞的细胞力学。使用激光共聚焦显微镜通过免疫技术分析了样本。在连接蛋白的空间排列方面发现了显著的统计学差异。然而，这些差异不是由于它们的表达。使用原子力显微镜比较了糖尿病和正常心肌细胞之间的固有细胞硬度，并获得了糖尿病活心肌细胞的第一个弹性图谱切片。获得的数据表明，糖尿病心肌细胞的硬度高于对照。本工作提供了实验证据，表明与细胞-细胞和细胞-细胞外基质通讯相关的细胞内变化发生，这可能与心脏致病机制有关。这些变化可能导致心肌细胞的机械和电学特性发生改变，从而导致糖尿病心肌病。心肌细胞蛋白的结构组织对于它们作为心脏收缩单位的有效功能至关重要。本工作表明，糖尿病可诱导连接蛋白、微管和闰盘的空间组织发生显著变化。我们获得了糖尿病活心肌细胞的第一个弹性图谱切片。结果显示，糖尿病和对照心肌细胞的图谱切片存在统计学差异，糖尿病心肌细胞比正常心肌细胞更硬。
