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 is involved in maintaining cardiovascular homeostasis. The expression and activity of Nos3 are regulated at transcriptional, post-transcriptional, and post-translational levels [3].

In adipocyte-specific Nos3 knockout (A-NOS3 KO) mice, despite less weight gain, there was a significant increase in blood pressure after high-fat diet (HFD) feeding, along with exacerbated vascular dysfunction, remodelling, and increased inflammation and hypoxia markers in perivascular adipose tissues (PVATs). Upregulation of chemerin, an adipokine linking obesity and vascular dysfunction, was also observed. Treatment with chemerin neutralizing antibody normalized the expression of remodelling markers, suggesting that Nos3 in adipocytes is vital for vascular homeostasis [1]. Also, ApoE/NOS3 double knockout mice developed hypertensive fundus retinopathy, hypertensive nephropathy, abnormal lipid levels, liver steatosis, and atherosclerotic lesions, making them a useful model for hypertension and atherosclerosis studies [2].

In conclusion, Nos3 plays a vital role in maintaining vascular homeostasis, especially in adipocytes. Gene knockout mouse models, such as A-NOS3 KO and ApoE/NOS3-KO mice, have been instrumental in revealing its role in obesity-induced vascular remodelling, hypertension, and atherosclerosis, providing valuable insights into the pathophysiology of these cardiovascular diseases.