Salem Esam S B, Fan Guo-Chang
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 5872 Care Mail Loc-0575, Cincinnati, OH, 45267, USA.
Adv Exp Med Biol. 2017;998:113-138. doi: 10.1007/978-981-10-4397-0_8.
Diabetic subjects are at risk of developing cardiovascular disease, which accounts for 60-80% of diabetes-related mortality. Atherosclerosis is still considered as a leading cause of heart failure in diabetic patients, but it could also be an intrinsic and long-term effect of contractile cardiac cells malfunction, known as diabetic cardiomyopathy (DCM). Pathologically, this cardiac dysfunction is manifested by inflammation, apoptosis, fibrosis, hypertrophy and altered cardiomyocytes metabolism. However, the underlying molecular mechanisms of DCM pathophysiology are not clearly understood. Recent and several studies have suggested that exosomes are contributed to the regulation of cell-to-cell communication. Therefore, their in-depth investigation can interpret the complex pathophysiology of DCM. Structurally, exosomes are membrane-bounded vesicles (10-200 nm in diameter), which are actively released from all types of cells and detected in all biological fluids. They carry a wide array of bioactive molecules, including mRNAs, none-coding RNAs (e.g., microRNAs, lncRNAs, circRNAs, etc), proteins and lipids. Importantly, the abundance and nature of loaded molecules inside exosomes fluctuate with cell types and pathological conditions. This chapter summarizes currently available studies on the exosomes' role in the regulation of diabetic cardiomyopathy. Specifically, the advances on the pathological effects of exosomes in diabetic cardiomyopathy as well as the therapeutic potentials and perspectives are also discussed.
糖尿病患者有患心血管疾病的风险,心血管疾病占糖尿病相关死亡率的60 - 80%。动脉粥样硬化仍然被认为是糖尿病患者心力衰竭的主要原因,但它也可能是收缩性心肌细胞功能障碍的一种内在的长期影响,即糖尿病性心肌病(DCM)。从病理角度来看,这种心脏功能障碍表现为炎症、细胞凋亡、纤维化、肥大以及心肌细胞代谢改变。然而,DCM病理生理学的潜在分子机制尚不清楚。最近的一些研究表明,外泌体有助于细胞间通讯的调节。因此,对外泌体的深入研究可以解释DCM复杂的病理生理学。从结构上讲,外泌体是膜结合囊泡(直径为10 - 200nm),由所有类型的细胞主动释放,并在所有生物体液中被检测到。它们携带各种各样的生物活性分子,包括mRNA、非编码RNA(如微小RNA、长链非编码RNA、环状RNA等)、蛋白质和脂质。重要的是,外泌体内所载分子的丰度和性质会随着细胞类型和病理状况而波动。本章总结了目前关于外泌体在糖尿病性心肌病调节中作用的现有研究。具体而言,还讨论了外泌体在糖尿病性心肌病中的病理作用以及治疗潜力和前景方面的进展。