Abstract 4341369: A newly developed model of atherosclerosis caused by the stress of metabolic syndrome in apolipoprotein E knockout mouse

Background: Atherosclerotic disease is influenced by multiple factors including hypertension, dyslipidemia, and diabetes. In clinical conditions, it is rarely due to a single pathology. Recently the global prevalence of metabolic syndrome has been steadily increasing, paralleled by a concomitant rise in atherosclerotic cardiovascular disease. Research Questions: The mechanisms underlying the progression of atherosclerotic complications in metabolic syndrome are not yet fully understood, necessitating further elucidation. Goals/Aims: In this study, we created a mouse model of metabolic syndrome by simultaneously reproducing hypertension, dyslipidemia, and glucose intolerance, and aimed to elucidate the mechanism of atherosclerosis in metabolic syndrome. Methods: Twelve-week-old male apolipoprotein E knockout mice were fed a high-fat diet to produce dyslipidemia, administered angiotensin II continuously to develop hypertension, and infused with streptozotocin intraperitoneally at 18 weeks to produce diabetes mellitus for metabolic syndrome (METS) mice. Control (CTL), high-fat diet alone (HFD), angiotensinll alone (ATll), and streptozotocin alone (STZ) mice were also produced and the results in the various groups were compared. Results: The METS group showed increased body weight, blood pressure, and serum total cholesterol. The METS group exhibited a significantly higher rate of atherosclerosis formation than the CTL group (METS; 25.7±11.6 %, CTL: 3.3±1.5 %, p<0.001). The expressions of nicotinamide adenine dinucleotide phosphate oxidase 2, nuclear factor-kappa B1, and matrix metalloproteinase-2 in the METS group were significantly higher than those in the CTL group by reverse transcription-polymerase chain reaction analysis. The METS model mouse showed severe atherosclerosis caused by oxidative stress, inflammation, and atherosclerotic plaque formation.