Lack of NPR1 Increases Vascular Endothelial Adhesion through Induction of Integrin Beta 4

• Published in: International journal of molecular sciences Vol. 23; no. 20; p. 12627
• Main Authors: Liu, Hongfei, Liu, Jiankun, Long, Changkun, Chen, Liping, Zhan, Wenxing, Xiao, Wanli, Gong, Xueting, Liu, Man, Tian, Xiao-Li, Chen, Shenghan
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.10.2022; MDPI
• Subjects: Aorta; Arteriosclerosis; Atherosclerosis; Blood pressure; Cardiovascular disease; Cell adhesion; Cell adhesion & migration; Coronary vessels; Cytokines; Endothelial cells; Endothelium; Gene expression; Genes; Homeostasis; Hypertension; integrin beta 4; Intercellular adhesion molecule 1; Microscopy; Monocytes; Nitric oxide; NPR1; Peptides; Permeability; Senescence; Sequence analysis; Signal transduction; Tumor necrosis factor-α; Umbilical vein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232012627

Natriuretic peptide receptor 1 (NPR1) serves as a modulator of vascular endothelial homeostasis. Interactions between monocytes and endothelial cells may initiate endothelium dysfunction, which is known as an early hallmark of atherosclerosis. In this study, we performed RNA-sequencing analysis for the aorta of Npr1 knockout (Npr1+/−) mice and found that differentially expressed genes were significantly related to cell adhesion. This result was supported by an increased expression of intercellular adhesion molecule 1 (ICAM-1) in the aortic endothelium of Npr1+/− mice. Moreover, we observed that the knockdown of NPR1 increased ICAM-1 expression and promoted THP-1 monocyte adhesion to human umbilical vein endothelial cells (HUVECs). NPR1 overexpression decreased ICAM-1 expression and inhibited the adhesion of monocytes to HUVECs treated by TNF-α (a cell adhesion inducer). Further analysis showed that adhesion-related genes were enriched in the focal adhesion signaling pathway, in which integrin beta 4 (Itgb4) was determined as a key gene. Notably, ITGB4 expression increased in vascular endothelium of Npr1+/− mice and in NPR1-knockdown HUVECs. The deficiency of ITGB4 decreased ICAM-1 expression and attenuated monocyte adhesion to NPR1-knockdown endothelial cells. Additionally, a reduced NPR1 and an increased ITGB4 expression level were found in an atherosclerosis mouse model. In conclusion, our findings demonstrate that NPR1 deficiency increases vascular endothelial cell adhesion by stimulating ITGB4 expression, which may contribute to the development of atherosclerosis.