We further characterized one of the transgenic strains, CETP-4, by optimizing the experimental condition for the mouse model of atherosclerosis, and found that it would be useful for the development of therapeutics against atherosclerosis.
To study the effects of diabetes on lipoprotein profiles and atherosclerosis in a rodent model, we crossed mice that express human apolipoprotein B (HuB), mice that have a heterozygous deletion of lipoprotein lipase (LPL1), and transgenic mice expressing human cholesteryl ester transfer protein (CETP).
To further elucidate the role of scavenger receptor class B type I (SR-BI) in reverse cholesterol transport and in atherogenesis, we performed studies in the rabbit, an animal model displaying a lipoprotein profile similar to that of human, expressing cholesteryl ester transfer protein in plasma and having been demonstrated to be susceptible to atherosclerosis.
This review discusses the potential of CETP inhibitors to protect against atherosclerosis in the context of the current knowledge of CETP function in both rodents and humans.
However, discussions regarding the role of CETP-mediated lipid transfer in the development of atherosclerosis and CETP inhibition as a potential strategy for prevention of atherosclerosis have been controversial.
To evaluate the impact of CETP expression on more advanced forms of atherosclerosis, we have cross-bred the human CETP transgene into the apoE knock-out (apoE0) background with and without concomitant expression of the human apo A-I transgene.
To investigate the role of macrophage CETP in atherosclerosis, LDL receptor knockout mice were transplanted with bone marrow from CETP transgenic mice, which express the human CETP transgene under control of its natural promoter and major regulatory elements.
CETP restores HDL-C levels in SR-BI(KO) mice, but it does not change the susceptibility to atherosclerosis and other typical characteristics that are associated with SR-BI disruption.
The cholesteryl ester transfer protein (CETP) has a central role in the lipid metabolism and therefore may alter the susceptibility to atherosclerosis.
We review the genetics of CETP and coronary disease, preclinical data on CETP inhibition and atherosclerosis, and the effects of CETP inhibition on cholesterol efflux and reverse cholesterol transport.
This study investigated whether the CETP gene I405V and Taq1B polymorphisms modified subclinical atherosclerosis in an asymptomatic Brazilian population sample.
Further studies are necessary for understanding of the role of CETP in lipid metabolism and the development of novel therapies involving a combination of strategies for treatment of atherosclerosis and cardiovascular disease.
Diet-induced atherosclerosis studies showed that testosterone deficiency increased by 100%, and CETP expression reduced by 44%, the size of aortic lesion area in castrated mice.
Cholesteryl ester transfer protein concentration is associated with progression of atherosclerosis and response to pravastatin in men with coronary artery disease (REGRESS).
These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells.
Ongoing phase 3 clinical trials with other CETP inhibitors may help to clarify if this strategy can ultimately be successful in the treatment of atherosclerosis.