The role of a murine transplantation model of atherosclerosis regression in drug
Authors Feig JE, Quick JS, Fisher EA
Submitted By Edward Fisher on 8/30/2012
Status Published
Journal Current opinion in investigational drugs (London, England : 2000)
Year 2009
Date Published 3/1/2009
Volume : Pages 10 : 232 - 238
PubMed Reference 19333880
Abstract Atherosclerosis is the leading cause of death worldwide. To date, the use of
statins to lower LDL levels has been the major intervention used to delay or
halt disease progression. These drugs have an incomplete impact on plaque burden
and risk, however, as evidenced by the substantial rates of myocardial
infarctions that occur in large-scale clinical trials of statins. Thus, it is
hoped that by understanding the factors that lead to plaque regression, better
approaches to treating atherosclerosis may be developed. A transplantation-based
mouse model of atherosclerosis regression has been developed by allowing plaques
to form in a model of human atherosclerosis, the apoE-deficient mouse, and then
placing these plaques into recipient mice with a normolipidemic plasma
environment. Under these conditions, the depletion of foam cells occurs.
Interestingly, the disappearance of foam cells was primarily due to migration in
a CCR7-dependent manner to regional and systemic lymph nodes after 3 days in the
normolipidemic (regression) environment. Further studies using this transplant
model demonstrated that liver X receptor and HDL are other factors likely to be
involved in plaque regression. In conclusion, through the use of this transplant
model, the process of uncovering the pathways regulating atherosclerosis
regression has begun, which will ultimately lead to the identification of new
therapeutic targets.

Investigators with authorship
Edward FisherNew York University School of Medicine