Affiliated Hospital of Nantong University, Nantong Laboratory of Development and Diseases, School of Life Science; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Jinxiang Zhao
Affiliated Hospital of Nantong University, Nantong Laboratory of Development and Diseases, School of Life Science; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China; Suqian First Hospital, Suqian, China
Jiehuan Xu
Affiliated Hospital of Nantong University, Nantong Laboratory of Development and Diseases, School of Life Science; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Bowen Li
Medical School, Nantong University, Nantong, China
Affiliated Hospital of Nantong University, Nantong Laboratory of Development and Diseases, School of Life Science; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Affiliated Hospital of Nantong University, Nantong Laboratory of Development and Diseases, School of Life Science; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Affiliated Hospital of Nantong University, Nantong Laboratory of Development and Diseases, School of Life Science; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
Artificially sweetened beverages containing noncaloric monosaccharides were suggested as healthier alternatives to sugar-sweetened beverages. Nevertheless, the potential detrimental effects of these noncaloric monosaccharides on blood vessel function remain inadequately understood. We have established a zebrafish model that exhibits significant excessive angiogenesis induced by high glucose, resembling the hyperangiogenic characteristics observed in proliferative diabetic retinopathy (PDR). Utilizing this model, we observed that glucose and noncaloric monosaccharides could induce excessive formation of blood vessels, especially intersegmental vessels (ISVs). The excessively branched vessels were observed to be formed by ectopic activation of quiescent endothelial cells (ECs) into tip cells. Single-cell transcriptomic sequencing analysis of the ECs in the embryos exposed to high glucose revealed an augmented ratio of capillary ECs, proliferating ECs, and a series of upregulated proangiogenic genes. Further analysis and experiments validated that reduced foxo1a mediated the excessive angiogenesis induced by monosaccharides via upregulating the expression of marcksl1a. This study has provided new evidence showing the negative effects of noncaloric monosaccharides on the vascular system and the underlying mechanisms.
