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 (essential) hypertension i s well-characterized in humans; however, the lack of an animal model that s imulates human disease hinders the elucidation of pathogenic mechanisms. We report here a transgenic atherosclerosis-polygenic hypertension model in D ahl salt-sensitive hypertensive rats that overexpress the human cholesteryl ester transfer protein (Tg[hCETP](DS)). Male Tg[hCETP](DS) rats fed regula r rat chow showed age-dependent severe combined hyperlipidemia, atheroscler otic lesions, myocardial infarctions and decreased survival. These findings differ from various mouse atherosclerosis models, demonstrating the necess ity of complex disease modeling in different species. The data demonstrate that cholesteryl ester transfer protein can be proatherogenic. The interact ion of polygenic hypertension and hyperlipidemia in the pathogenesis of ath erosclerosis in Tg[hCETP](DS) rats substantiates epidemiological observatio ns in humans.