Department of Physiology, HeartOtago, University of Otago, Dunedin, New Zealand.
Centre for Bioengineering and Nanomedicine (Dunedin), University of Otago, Dunedin, New Zealand.
J Diabetes Complications. 2020 Aug;34(8):107613. doi: 10.1016/j.jdiacomp.2020.107613. Epub 2020 May 4.
Diabetes is a chronic disease, characterized by hyperglycemia, which refers to the elevated levels of glucose in the blood, due to the inability of the body to produce or use insulin effectively. Chronic hyperglycemia levels lead to macrovascular and microvascular complications. The macrovascular complications consist of peripheral artery disease (PAD), cardiovascular diseases (CVD) and cerebrovascular diseases, while the microvascular complications comprise of diabetic microangiopathy, diabetic nephropathy, diabetic retinopathy and diabetic neuropathy. Vascular endothelial dysfunction plays a crucial role in mediating both macrovascular and microvascular complications under hyperglycemic conditions. In diabetic microvasculature, the intracellular hyperglycemia causes damage to the vascular endothelium through - (i) activation of four biochemical pathways, namely the Polyol pathway, protein kinase C (PKC) pathway, advanced glycation end products (AGE) pathway and hexosamine pathway, all of which commutes glucose and its intermediates leading to overproduction of reactive oxygen species, (ii) dysregulation of growth factors and cytokines, (iii) epigenetic changes which concern the changes in DNA as a response to intracellular changes, and (iv) abnormalities in non-coding RNAs, specifically microRNAs. This review will focus on gaining an understanding of the molecular complexities underlying the vascular complications in diabetes mellitus, to increase our understanding towards the development of new mechanistic therapeutic strategies to prevent or treat diabetes-induced vascular complications.
糖尿病是一种慢性疾病，其特征是高血糖，即由于身体无法有效产生或利用胰岛素，导致血液中的葡萄糖水平升高。慢性高血糖水平会导致大血管和微血管并发症。大血管并发症包括外周动脉疾病（PAD）、心血管疾病（CVD）和脑血管疾病，而微血管并发症包括糖尿病性微血管病变、糖尿病肾病、糖尿病性视网膜病变和糖尿病性神经病变。血管内皮功能障碍在高血糖条件下介导大血管和微血管并发症中起着至关重要的作用。在糖尿病性微血管中，细胞内高血糖通过以下方式对血管内皮造成损害：（i）四种生化途径的激活，即多元醇途径、蛋白激酶 C（PKC）途径、晚期糖基化终产物（AGE）途径和己糖胺途径，所有这些途径都将葡萄糖及其中间产物转化为活性氧的过度产生；（ii）生长因子和细胞因子的失调；（iii）表观遗传变化，即 DNA 作为对细胞内变化的响应而发生的变化；以及（iv）非编码 RNA，特别是 microRNAs 的异常。本综述将重点探讨理解糖尿病血管并发症背后的分子复杂性，以增加我们对开发新的机制治疗策略以预防或治疗糖尿病引起的血管并发症的理解。
