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Updated: Mar 3, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Atherogenesis and metabolic dysregulation in LDL receptor-knockout rats
Abstract:
Mechanisms of atherogenesis have been studied extensively in genetically engineered mice with disturbed cholesterol metabolism such as those lacking either the LDL receptor (Ldlr) or apolipoprotein E (apoe). Few other animal models of atherosclerosis are available. WT rabbits or rats, even on high-fat or high-cholesterol diets, develop sparse atherosclerotic lesions. We examined the effects of Ldlr deletion on lipoprotein metabolism and atherosclerotic lesion formation in Sprague-Dawley rats. Deletion of Ldlr resulted in the loss of the LDLR protein and caused a significant increase in plasma total cholesterol and triglycerides. On normal chow, Ldlr-KO rats gained more weight and were more glucose intolerant than WT rats. Plasma proprotein convertase subtilisin kexin 9 (PCSK9) and leptin levels were higher and adiponectin levels were lower in KO than WT rats. On the Western diet, the KO rats displayed exaggerated obesity and age-dependent increases in glucose intolerance. No appreciable aortic lesions were observed in KO rats fed normal chow for 64 weeks or Western diet for 16 weeks; however, after 34-52 weeks of Western diet, the KO rats developed exuberant atherosclerotic lesions in the aortic arch and throughout the abdominal aorta. The Ldlr-KO rat may be a useful model for studying obesity, insulin resistance, and early-stage atherosclerosis.
Insights
Genetically engineered rats lacking the LDL receptor (Ldlr) develop obesity and insulin resistance. These Ldlr-knockout rats also develop significant atherosclerotic lesions, offering a new model for studying cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Metabolic Disease Research
- Animal Models
Background:
- Atherosclerosis research relies heavily on genetically engineered mice, but other models are scarce.
- Standard rodent models show limited atherosclerotic lesion development, even with high-fat diets.
Purpose of the Study:
- To investigate the impact of LDL receptor (Ldlr) deletion on lipoprotein metabolism and atherosclerosis in Sprague-Dawley rats.
- To establish a novel rat model for studying obesity, insulin resistance, and atherosclerosis.
Main Methods:
- Generated LDL receptor knockout (Ldlr-KO) Sprague-Dawley rats.
- Administered normal chow or Western diet.
- Monitored weight gain, glucose intolerance, plasma lipids, PCSK9, leptin, and adiponectin.
- Assessed atherosclerotic lesion development in the aorta.
Main Results:
- Ldlr-KO rats exhibited increased plasma total cholesterol and triglycerides, obesity, and glucose intolerance compared to wild-type (WT) rats.
- KO rats showed elevated PCSK9 and leptin, and reduced adiponectin levels.
- Significant atherosclerotic lesions developed in the aortic arch and abdominal aorta of KO rats after 34-52 weeks on a Western diet.
Conclusions:
- Ldlr-KO rats represent a valuable new model for studying diet-induced obesity, insulin resistance, and atherosclerosis.
- This model provides a platform for investigating the mechanisms underlying these interconnected conditions.
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