ApoE/NOS3 Knockout Mice as a Novel Cardiovascular Disease Model of Hypertension and Atherosclerosis

Hypertension is an independent risk factor for atherosclerosis. However, few models of hypertensive atherosclerosis have been established in medical research. In this study, we crossed the ApoE knockout (ApoE-KO; ApoE-/-) atherosclerotic mouse model with the NOS3 knockout (NOS3-KO; NOS3-/-) hypertensive mouse model to establish an ApoE/NOS3 double knockout (ApoE/NOS3-KO; ApoE/NOS3-/-) hypertensive atherosclerosis mouse model. We found that ApoE/NOS3-/- mice reproduced normally, had a blood pressure of 133.00 ± 3.85 mmHg, and developed hypertensive fundus retinopathy and hypertensive nephropathy. In addition, serum total cholesterol (TC) and low-density lipoprotein (LDL) levels in the blood were abnormally elevated, steatosis was observed in the liver cells, and atherosclerotic lesions were observed in the aortic vessels in ApoE/NOS3-/- adult mice. In conclusion, ApoE/NOS3-/- adult mice are a satisfactory model of hypertension and atherosclerosis and can be utilized for studies on cardiovascular diseases.