MechanismsLandmark
Human CETP overexpression in hypertensive Dahl rats spontaneously causes combined hyperlipidemia, myocardial infarction and reduced survival, proving CETP can be proatherogenic (Nat Med 1999)
Original title: Spontaneous combined hyperlipidemia, coronary heart disease and decreased survival in Dahl salt-sensitive hypertensive rats transgenic for human cholesteryl ester transfer protein
The acceleration of atherosclerosis by polygenic hypertension is well characterised in humans, but a lack of animal models simulating this disease has hindered mechanistic study. The authors created a transgenic atherosclerosis-polygenic-hypertension model, Dahl salt-sensitive hypertensive rats overexpressing human cholesteryl ester transfer protein (Tg[hCETP]DS). Male Tg[hCETP]DS rats fed regular chow spontaneously developed age-dependent severe combined hyperlipidemia, atherosclerotic lesions, myocardial infarctions and decreased survival. These findings differed from various mouse atherosclerosis models, demonstrating the need for complex disease modeling across species. The data show cholesteryl ester transfer protein can be proatherogenic, and the interaction of polygenic hypertension and hyperlipidemia in Tg[hCETP]DS rats substantiates epidemiological observations in humans.
Original abstract
The acceleration of atherosclerosis by polygenic (essential) hypertension is well-characterized in humans; however, the lack of an animal model that simulates human disease hinders the elucidation of pathogenic mechanisms. We report here a transgenic atherosclerosis-polygenic hypertension model in Dahl salt-sensitive hypertensive rats that overexpress the human cholesteryl ester transfer protein (Tg[hCETP]DS). Male Tg[hCETP]DS rats fed regular rat chow showed age-dependent severe combined hyperlipidemia, atherosclerotic lesions, myocardial infarctions and decreased survival. These findings differ from various mouse atherosclerosis models, demonstrating the necessity of complex disease modeling in different species. The data demonstrate that cholesteryl ester transfer protein can be proatherogenic. The interaction of polygenic hypertension and hyperlipidemia in the pathogenesis of atherosclerosis in Tg[hCETP]DS rats substantiates epidemiological observations in humans.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.