Mouse models for atherosclerosis and pharmaceutical modifiers.
Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in humans. The mouse is the most useful, economic, and valid model for studying atherosclerosis and exploring effective therapeutic approaches. Among the most widely used mouse models for atherosclerosis are apolipoprotein E-deficient (ApoE-/-) and LDL receptor-deficient (LDLr-/-) mice. An up-and-coming model is the ApoE*3Leiden (E3L) transgenic mouse. Here, we review studies that have explored how and to what extent these mice respond to compounds directed at treatment of the risk factors hypercholesterolemia, hypertriglyceridemia, hypertension, and inflammation. An important outcome of this survey is that the different models used may differ markedly from one another in their response to a specific experimental manipulation. The choice of a model is therefore of critical importance and should take into account the risk factor to be studied and the working spectrum of the compounds tested.
Zadelaar
Susanne
S
TNO Quality of Life, Gaubius Laboratory, Department of Biosciences, P.O. Box 2215, 2301 CE Leiden, The Netherlands.
Kleemann
Robert
R
Verschuren
Lars
L
de Vries-Van der Weij
Jitske
J
van der Hoorn
José
J
Princen
Hans M
HM
Kooistra
Teake
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D050171:Dyslipidemias / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012680:Sensitivity and Specificity
D000959:Antihypertensive Agents; D001057:Apolipoproteins E; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents