1. Complement Factor C1q Mediates Vascular Endothelial Dysfunction in STZ-Induced Diabetic Mice.
- Author
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Mao, Aiqin, Li, Zicheng, Shi, Xiaoming, Zhang, Ka, Kan, Hao, Geng, Li, and He, Dongxu
- Subjects
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VASCULAR endothelial cells , *DIABETES complications , *ENDOTHELIUM diseases , *REACTIVE oxygen species , *MUSCLE cells - Abstract
Diabetes is a significant global public health issue with implications for vascular endothelial cells (ECs) dysfunction and the subsequent development and advancement of diabetes complications. This study aims to compare the cellular and molecular properties of the aorta in normal and streptozotocin (STZ)-induced diabetic mice, with a focus on elucidating potential mechanism underlying EC dysfunction. Here, we performed a single-cell RNA sequencing survey of 32,573 cells from the aorta of normal and STZ-induced diabetic mice. We found a compendium of 10 distinct cell types, mainly ECs, smooth muscle cells, fibroblast, pericyte, immune cells, and stromal cells. As the diabetes condition progressed, we observed a subpopulation of aortic ECs that exhibited significantly elevated expression of complement (C) molecule C1qa compared with their healthy counterparts. This increased expression of C1qa was found to induce reactive oxygen species (ROS) production, facilitate EC migration and increased permeability, and impair the vasodilation within the aortic segment of mice. Furthermore, AAV-Tie2-shRNA-C1qa was administered into diabetic mice by tail vein injection, showing that inhibition of C1qa in the endothelium led to a reduction in ROS production, decreased vascular permeability, and improved vasodilation. Collectively, these findings highlight the crucial involvement of C1qa in endothelial dysfunction associated with diabetes. Article Highlights: The molecular mechanisms and cellular heterogeneity of C1q in endothelial cells, which regulate vascular function, remain unclear. C1q is involved in the regulation of vascular function. C1q in vascular endothelial cells can regulate vascular function, including permeability, immunity, and diastolic function. C1q represents a promising therapeutic target for the treatment of endothelial dysfunction associated with diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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