16 August 2018

CUHK Study Reveals Novel Mechanism that Contributes to Vascular Endothelial Dysfunction in Diabetes



A research team led by Prof. Huang Yu of the School of Biomedical Sciences and Director of the Institute of Vascular Medicine, Faculty of Medicine at The Chinese University of Hong Kong (CUHK), has recently revealed a cell-to-cell communication mechanism that contributes to vascular endothelial dysfunction in diabetes. Based on the studies made on diabetic mice, the team has found that an enzyme “arginase 1” was enriched in serum exosomes and transferred to endothelial cells, thus impairing endothelial function. The finding has been published in Proceedings of the National Academy of Sciences (PNAS).

One in ten people in Hong Kong has type II diabetes mellitus. Long-term high blood sugar level causes vascular endothelial dysfunction, an important pathological event leading to diabetic vascular complications. According to research conducted by The World Health Organization (WHO), about half of diabetics die from cardiovascular complications. The US Centers for Disease Control and Prevention also reported that adults with diabetes are nearly twice as likely to die from heart disease or stroke as people without diabetes.

The inner linings of blood vessels are formed by endothelial cells, which are responsible for controlling blood pressure and coagulation. These cells are directly exposed to circulating substances/microvesicles in the blood, including serum exosomes. Serum exosomes are endosome-derived nanoscale membrane vesicles released into the bloodstream and other extracellular fluid compartments. A surge of research interest has been recently directed to exosomes because they transport contents such as proteins, and microRNAs (miRNAs) to recipient cells via the bloodstream, representing a new communication route between cells. Through some of these functional molecules, exosomes participate in a broad spectrum of physiological and pathological processes, including immune reaction, tumor metastasis, infectious disease, and so on. Growing evidence has revealed alterations of exosomal contents, mostly miRNAs, in diabetes and obesity, indicating a pathogenic role in such alterations. However, how endothelial cells respond to serum exosomes and the implications in diabetic vasculopathy have never been explored.

In this very first study, Prof. Huang’s team unraveled, with potential clinical relevance, the previously undefined importance of serum exosomes in regulating endothelial function and vascular homeostasis. The comparative proteomics analysis showed that diabetic mouse serum exosomes contain high level of enzyme “arginase 1” and the enzyme was delivered to endothelial cells. “Arginase 1” inhibits the production of nitric oxide (NO), which is essential in maintaining vascular homeostasis.

Prof. Huang remarked, “Understanding how exosomal contents impact vascular function will provide new insights into mechanisms by which diabetes causes blood vessel damage and new ways of detecting early stages of this damage. This cell-to-cell communication mechanism may also contribute to vascular dysfunction under other pathogeneses such as hypertension and dyslipidemia. Prof. Huang’s team is now collaborating with clinical colleagues in the Prince of Wales Hospital to explore the prognostic value of circulating microvesicles in human cardio-metabolic diseases.”

Prof. Huang’s team mainly focuses on vascular endothelial cell signalling, the pathogenesis of cardio-metabolic diseases and the elucidation of new pharmacological effects of drugs used in the treatment of cardiovascular complications. His team has in recent years published a series of important studies in Nature, Cell Metabolism, Circulation Research, European Heart Journal, Diabetes and many other high impact research journals in the fields of cardio-metabolic biology and medicine. His research greatly advances people’s understanding of the pathophysiological process of endothelial dysfunction in hypertension, obesity and diabetes. Prof. Huang received the Croucher Senior Research Fellow Award in 2014 and the Natural Science Award (2nd class) in 2015 from the Ministry of Science and Technology and in 2017 from the Ministry of Education.

Research team from the School of Biomedical Sciences of the Faculty of Medicine at CUHK reveals a cell-to-cell communication mechanism that contributes to vascular endothelial dysfunction in diabetes. 
(From left) Prof. HUANG Yu and his team members HUANG Yuhong, WANG Yifan and LAU Chi Wai.
Research team from the School of Biomedical Sciences of the Faculty of Medicine at CUHK reveals a cell-to-cell communication mechanism that contributes to vascular endothelial dysfunction in diabetes.
(From left) Prof. HUANG Yu and his team members HUANG Yuhong, WANG Yifan and LAU Chi Wai.