Establishment of a rat model with diet-induced coronary atherosclerosis

Abstract

Coronary atherosclerotic disease is a serious disease in humans, but no suitable animal model is available currently for further studies. We used apolipoprotein E gene knockout (ApoE KO) rats to induce hypercholesterolemia through a special high cholesterol/bile salt diet (Paigen diet), then analyzed aortic and coronary atherosclerosis lesions and the myocardial injury in order to establish a novel small animal model of coronary atherosclerosis. Plasma cholesterol of ApoE KO rats increased 7.6-fold compared with wild-type rats after 8 weeks on the Paigen diet. After 10 to 12 weeks of subsisting on the Paigen diet, ApoE KO rats developed mild aortic atherosclerosis with severe coronary atherosclerosis. Hematoxilyn and eosin staining showed that 11 out of 12 ApoE KO male rats had right coronary artery atherosclerosis, 7 of them were>70% occluded. Oil Red O (Lipid Stain), Mac2 immuno-staining and Masson’s trichrome staining demonstrated substantial amounts of lipid, macrophages and collagen fibers in coronary atherosclerosis plaques. In addition, ApoE KO male rats had severe myocardial focal lesions with cholesterol ester as the main component in the lesions. In conclusion, ApoE KO rats developed severe hypercholesterolemia, coronary atherosclerosis and myocardial cholesterol ester deposition after subsisting on the Paigen diet and can be used as a novel animal model for studies on cholesterol metabolism and coronary atherosclerotic disease.

Dare to Compare. Development of Atherosclerotic Lesions in Human, Mouse, and Zebrafish

“…Another imaging technique, that allows to calculate blood flow based on Doppler blood velocity and vessel diameter as well as detection of atherosclerotic plaques is the multifrequency UBM combined with Doppler ultrasound (132). Readout quality from UBMs is frequently increasing, enabling reliable diagnosis of small animals with higher heart rates and smaller vessel sizes (133)(134)(135)(136). Nevertheless, interpretation of the acquired data requires even more experience.…”

“…The major apolipoprotein in chylomicrons, Apolipoprotein E (ApoE), can serve as a ligand for the LDL receptor (LDLR). Synthesis of ApoE occurs in the brain, liver, and other tissues in both humans and mice, although humans have high-density lipoprotein (HDL) subsets and ApoE isoforms that mice lack (56,57). In addition to its effects on lipoprotein metabolism, ApoE has roles in macrophage biology, immune function, and adipose tissue biology (56,58).…”

Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR−/− mice fed on high-fat diet

“…For atherosclerosis analysis, after being visualized by Oil-red O staining, lesion area in en face aorta was then measured by Image J Graphic Analysis System. The quantification of the aortic root was performed on aorta cross sections as what we had previously described 27 . Briefly, we used OCT to embed the heart, and then put it in liquid nitrogen for making it snap-frozen and stored it at −30 °C before sectioning.…”

Pterostilbene reduces endothelial cell apoptosis by regulation of the Nrf2‑mediated TLR‑4/MyD88/NF‑κB pathway in a rat model of atherosclerosis

“…All surgeries were performed under anesthesia with pentobarbital (40 mg/kg), and efforts were made to minimize suffering of the rats. The rats were fed a 2.5% cholesterol diet for 8 weeks as described previously ( 26 ). The rats were randomly divided into three experimental groups: healthy group (n=6); group that received phosphate-buffer saline (PBS) treatment (n=10); group that orally received pterostilbene ( trans -3,5-dimethoxy-4'-hydroxystilbene, C 16 H 16 O 3 , ≥99%, purity; 10 mg/kg/day; Great Forest Biomedical, Hangzhou, China; n=10) treatment once a day.…”