image: The basilar artery and coronary artery in the brain of an ApoE homozygous mutant dog are narrowed and occluded due to severe arteriosclerosis. view more
Credit: ©Science China Press
A research group led by Dr. Zhang Yongqing from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, reported that ApoE knockout dogs showed severe arteriosclerosis, mimicking human cerebrovascular disease.
As people's living standards improve and their eating habits change, stroke and coronary artery disease caused by arteriosclerosis have become the leading causes of death worldwide. Dyslipidemia is a major contributor for arteriosclerosis, and apolipoprotein E (ApoE) plays a key role in cholesterol metabolism. The ApoE mutant mice and rats showing elevated cholesterol levels have been widely used for arteriosclerosis study. However, these animal models rarely exhibit severe arteriosclerosis and patients related clinical symptoms, limiting their use in translational research. Dogs are anatomically, physiologically, and metabolically closer to humans than mice, making them potentially ideal models for cerebrovascular disease.
Zhang Yongqing Group, together with Beijing SINOGENE Biotechnology Company, Professor Ji Xunming from Beijing Xuanwu Hospital, Professor Liu Enqi from Xi'an Jiaotong University Medical College and so on revealed that ApoE knockout dogs exhibit extensive and severe arteriosclerosis plaques, arterial stenosis and occlusion, thrombosis, and, ultimately, stroke and gangrene by Magnetic Resonance Imaging, ultrasonic diagnosis, and multi-omic analysis. The most important clinical consequences of arteriosclerosis in humans are lesions in the cerebral arteries and coronary arteries, which are fully replicated in adult mutant dogs. More importantly, the homozygous F2 and F3 offspring showed evidence of hypercholesterolemia and severe atherosclerosis consistent with founder mutants. These results suggest that the ApoE mutants may be useful for basic and translational research in arteriosclerosis and related diseases. Arteriosclerosis and related strokes in dogs can be examined using noninvasive MRI and ultrasound analyses commonly used in hospitals to assess disease progression and prognosis.
This work is supported by the National Natural Science Foundation of China (NSFC; grant number 81620108011, 31830036 and 31921002), the Ministry of Science and Technology of China (MOST; 2017YFC1308401), the Beijing Municipal Science & Technology Commission (Z181100001518001), MOST (2019YFA0707100), and the Chinese Academy of Sciences (XDBS1020100).
See the article:
Zhao, H., Zhao, J., Wu, D., et al. (2021). Dogs lacking Apolipoprotein E show advanced atherosclerosis leading to apparent clinical complications. Sci China Life Sci, in press, https://doi.org/10.1007/s11427-021-2006-y.
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Science China Life Sciences