Mouse Models of Experimental Atherosclerosis as a Tool for Checking a Putative Anti-Atherogenic Action of Drugs

Jawień, Jacek

doi:10.5772/26071

Cited by 1 publication

(1 citation statement)

References 119 publications

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“…eNOX5 does not aggravate atherosclerosis in ApoE −/− mice with and without diabetes. Mice deficient in apo E (ApoE −/− mice) spontaneously develop atherosclerosis 21,22 . Therefore, eNOX5 ki/ki mice were crossed with ApoE −/− mice to test the role of Nox5 under aggravated conditions.…”

Section: Resultsmentioning

confidence: 99%

Endothelial reactive oxygen-forming NADPH oxidase 5 is a possible player in diabetic aortic aneurysm but not atherosclerosis

Watson

Elbatreek

et al. 2022

Sci Rep

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Atherosclerosis and its complications are major causes of cardiovascular morbidity and death. Apart from risk factors such as hypercholesterolemia and inflammation, the causal molecular mechanisms are unknown. One proposed causal mechanism involves elevated levels of reactive oxygen species (ROS). Indeed, early expression of the ROS forming NADPH oxidase type 5 (Nox5) in vascular endothelial cells correlates with atherosclerosis and aortic aneurysm. Here we test the pro-atherogenic Nox5 hypothesis using mouse models. Because Nox5 is missing from the mouse genome, a knock-in mouse model expressing human Nox5 in its physiological location of endothelial cells (eNOX5ki/ki) was tested as a possible new humanised mouse atherosclerosis model. However, whether just on a high cholesterol diet or by crossing in aortic atherosclerosis-prone ApoE−/− mice with and without induction of diabetes, Nox5 neither induced on its own nor aggravated aortic atherosclerosis. Surprisingly, however, diabetic ApoE−/− x eNOX5ki/ki mice developed aortic aneurysms more than twice as often correlating with lower vascular collagens, as assessed by trichrome staining, without changes in inflammatory gene expression, suggesting that endothelial Nox5 directly affects extracellular matrix remodelling associated with aneurysm formation in diabetes. Thus Nox5-derived reactive oxygen species are not a new independent mechanism of atherosclerosis but may enhance the frequency of abdominal aortic aneurysms in the context of diabetes. Together with similar clinical findings, our preclinical target validation opens up a first-in-class mechanism-based approach to treat or even prevent abdominal aortic aneurysms.

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Section: Resultsmentioning

confidence: 99%