Advancing age increases the size and severity of spontaneous atheromas in mouse models of atherosclerosis

Abstract

Using multiple mouse models, we explored the impact of aging on the size and severity of atherosclerotic lesions. In young, middle-aged and old apolipoprotein E knockout mice (ApoE−/−) fed an atherogenic diet (AD) for 3–8 weeks, plaque/atheroma formation in the descending aorta and aortic root, and atheroma development in the carotid in response to partial carotid ligation (PCL) were assessed. Total and LDL cholesterol, and triglycerides were higher in old compared to both other age groups, regardless of AD duration. Aortic plaque burden increased with AD duration in all ages. The size and plaque morphology grade of aortic root atheromas was higher with age; however, there was no effect of age on the size or severity of carotid atheromas after PCL. We additionally induced hyperlipidemia in young and old C57BL/6 mice by adeno-associated virus mediated upregulation of LDL receptor regulator, Pcsk9, and 5 weeks of AD. Despite lower cholesterol in old compared to young Pcsk9 mice, there was a greater size and severity of aortic root atheromas in old mice. However, like the ApoE−/− mice, there was no effect of age on size or severity of PCL-induced carotid artery atheromas in Pcsk9 mice. Together, these results suggest that aging increases the size and severity of spontaneous aortic atheromas.

Mitochondrial DNA leakage triggers inflammation in age-related cardiovascular diseases

“…Its main feature is lipids depositing in the arterial intima and form into plaques, which leads to reduced blood flow. Plaques rupture can also cause thrombosis and acute complications ( Gogulamudi et al, 2023 ). The pathology of atherosclerosis is complex, including foam cells forming, atherosclerotic plaque forming and rupture, calcification, and thrombus formation.…”

LXR Agonist T0901317′s Hepatic Impact Overrules Its Atheroprotective Action in Macrophages, Driving Early Atherogenesis in Chow-Diet-Fed Male Apolipoprotein E Knockout Mice

“…Therefore, our current findings should be followed up with studies on the impact of LXR agonist treatment on the progression and/or regression of established, more inflammatory, and necrotic atherosclerotic lesions. Replication of our experiment in mice with a higher age at the start of the study may also be required, since Gogulamudi et al [37] showed that age can significantly affect the atherogenic dietfeeding-associated hypercholesterolemia extent and lesion development outcome in APOE knockout mice. Furthermore, although we do not anticipate that the gender of the mice will significantly affect the overall impact of T0901317 s actions, it is recommended to perform future studies in both male and female mice.…”

Adaptive immunity and atherosclerosis: aging at its crossroads

“…It has been shown previously that aging promotes atherosclerosis development in low density lipoprotein receptor (Ldlr) deficient mice as well as in Apolipoprotein E (ApoE) deficient mice ( 15 – 17 ). Similarly, C57BL/6 mice treated with PCSK9-AAV to induce hypercholesterolemia at advanced age, show increased atherosclerosis development compared to their young counterparts ( 18 ). Particularly in chow-diet fed aged Ldlr -/- mice, plaques gradually developed in the context of mild hypercholesterolemia, and show human-like plaque features such as fibrosis and calcification ( 15 ).…”