Genetics
A moderate-expresser human-CETP transgenic rat model recapitulates female athero-resistance seen in humans (Atherosclerosis 2004)
Original title: Analysis of gender-specific atherosclerosis susceptibility in transgenic[hCETP]25DS rat model
To model the well-documented sex difference in atherosclerosis susceptibility, a moderate-expresser line transgenic for human CETP (Tg25) was developed in the Dahl salt-sensitive hypertensive rat strain, with identical genetic background, environmental factors, and equivalent hepatic CETP RNA levels confirmed between sexes. Tg25 male rats showed worse hypercholesterolemia, hypertriglyceridemia, coronary plaques, and survival outcomes than Tg25 females. Hepatic transcription profiles of Tg25 males and females, each normalized to their respective gender- and age-matched non-transgenic controls, differed significantly, with hierarchical cluster analysis and quantitative real-time RT-PCR pointing to pathways involved in inflammation and arachidonic acid epoxygenation, not just cholesterol metabolism, as associated with coronary plaque progression. The authors conclude that gender-specific factors are key modulators of atherosclerosis phenotype in this model, and suggest a possible role for the liver as a source of systemic proatherogenic factors.
Original abstract
Epidemiological and clinical data demonstrate differences in atherosclerotic coronary heart disease prevalence between age-matched men and premenopausal women. Mechanisms underlying relative athero-susceptibility in men and athero-resistance in premenopausal women remain to be elucidated. Lack of informative animal models hinders research. We report here a moderate-expresser line transgenic for human cholesteryl ester transfer protein (CETP) in the Dahl salt-sensitive hypertensive rat strain, Tg25, that recapitulates premenopausal female athero-resistance. Having ascertained identical genetic background, environmental factors, and equivalent CETP hepatic RNA levels, we detect worse hypercholesterolemia, hypertriglyceridemia, coronary plaques and survival outcome in Tg25 male rats compared with Tg25 females. Hepatic transcription profiles of Tg25 males and females normalized to respective gender- and age-matched non-transgenic controls exhibit significant differences. Genes implicated on hierarchical cluster analysis and quantitative real-time RT-PCR pinpoint pathways associated with coronary plaque progression such as inflammation and arachidonic acid epoxygenation, and not just cholesterol metabolism pathways. The data demonstrate gender-specific factors as key modulators of atherosclerosis phenotype and suggest a possible role for the liver in atheroma progression as a large organ source of proatherogenic systemic factors.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.