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Analysis of gender-specific atherosclerosis susceptibility in transgenic[hCETP]25DS rat model.

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.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Herrera VL,Tsikoudakis A,Didishvili T,Ponce LR,Bagamasbad P,Gantz D,Herscovitz H,Van Tol A,Ruiz-Opazo N

doi

10.1016/j.atherosclerosis.2004.06.017

keywords:

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

9-18

issue

1

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(04)00367-3

journal_volume

177

pub_type

杂志文章

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