A newly developed model of atherosclerosis caused by the stress of metabolic syndrome in apolipoprotein E knockout mouse
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Atherosclerotic disease is influenced by multiple factors including hypertension, dyslipidemia, and diabetes and it is rarely due to a single pathology in clinical conditions. In this study, we created a mouse model of metabolic syndrome 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, angiotensin II alone, and streptozotocin alone 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.
Conclusions
The METS model mouse showed severe atherosclerosis caused by oxidative stress, inflammation, and atherosclerotic plaque formation. This model is expected to be useful as a model that more closely resembles the pathophysiology of clinical atherosclerosis.
Perspective
What Is New?
This study introduces a novel metabolic syndrome mouse model that closely resembles human atherosclerosis by integrating hypertension, dyslipidemia, and diabetes into an apolipoprotein E knockout mouse.
What Are the Clinical Implications?
The metabolic syndrome mouse model demonstrates severe atherosclerosis driven by oxidative stress and inflammation, making it a valuable tool for testing therapeutic strategies targeting metabolic syndrome-related cardiovascular diseases.
