Nos3, also known as endothelial nitric oxide synthase (eNOS), is a crucial enzyme in the cardiovascular system. It synthesizes nitric oxide (NO) from L-arginine, which serves as an important vasodilator and plays a vital role in maintaining cardiovascular homeostasis. NOS3 expression and activity are regulated at transcriptional, post-transcriptional, and post-translational levels [3].

In a study using adipocyte-specific NOS3 knockout (A-NOS3 KO) mice, despite less weight gain, these mice showed a significant increase in blood pressure after high-fat diet (HFD) feeding, along with exacerbated vascular dysfunction and remodelling. This indicates that NOS3 in adipocytes is essential for maintaining vascular homeostasis, and its dysfunction contributes to obesity-induced vascular remodelling and hypertension [1]. Another study established an ApoE/NOS3 double knockout mouse model. ApoE/NOS3 -/- mice developed hypertensive fundus retinopathy, hypertensive nephropathy, abnormal elevation of serum cholesterol, and atherosclerotic lesions, suggesting it is a useful model for studying hypertension and atherosclerosis [2].

In conclusion, Nos3 is vital for cardiovascular homeostasis. Gene knockout mouse models, such as A-NOS3 KO and ApoE/NOS3 -/- mice, have been instrumental in revealing its role in obesity-related hypertension, vascular remodelling, and atherosclerotic disease. These findings enhance our understanding of the biological functions of Nos3 and its implications in disease pathogenesis.

References:

1. Man, Andy W C, Zhou, Yawen, Reifenberg, Gisela, Xia, Ning, Li, Huige. . Deletion of adipocyte NOS3 potentiates high-fat diet-induced hypertension and vascular remodelling via chemerin. In Cardiovascular research, 119, 2755-2769. doi:10.1093/cvr/cvad164. https://pubmed.ncbi.nlm.nih.gov/37897505/

2. Liu, Ke, Chen, Bangzhu, Zeng, Fanwen, Yan, Jiarong, Zhang, Shouquan. 2022. ApoE/NOS3 Knockout Mice as a Novel Cardiovascular Disease Model of Hypertension and Atherosclerosis. In Genes, 13, . doi:10.3390/genes13111998. https://pubmed.ncbi.nlm.nih.gov/36360235/

3. Oliveira-Paula, Gustavo H, Lacchini, Riccardo, Tanus-Santos, Jose E. 2015. Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms. In Gene, 575, 584-99. doi:10.1016/j.gene.2015.09.061. https://pubmed.ncbi.nlm.nih.gov/26428312/