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Mouse models for atherosclerosis and pharmaceutical modifiers

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Author: Zadelaar, A.S.M. · Kleemann, R. · Verschuren, L. · Vries-van der Weij, J. de · Hoorn, J. van der · Princen, H.M. · Kooistra, T.
Institution: TNO Kwaliteit van Leven
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 8, 27, 1706-1721
Identifier: 240117
doi: doi:10.1161/ATVBAHA.107.142570
Keywords: Biology · Biomedical Research · ACE inhibitors · AT1 receptor antagonists · Atherosclerosis · LXR · Mouse models · Pharmaceutical drugs · PPAR · Statins · atorvastatin · avasimibe · candesartan · captopril · cholesterol acyltransferase inhibitor · dipeptidyl carboxypeptidase inhibitor · hydralazine · hydroxymethylglutaryl coenzyme A reductase inhibitor · irbesartan · losartan · ly 465608 · n (2,2,2 trifluoroethyl) n [4 [2,2,2 trifluoro 1 hydroxy 1 (trifluoromethoxy)ethyl]phenyl]benzenesulfonamide · olmesartan · perindopril · peroxisome proliferator activated receptor alpha agonist · pirinixic acid · pitavastatin · pravastatin · quinapril · ramipril · rosuvastatin · simvastatin · telmisartan · temocapril · unindexed drug · valsartan · zofenopril · antihypertensive agent · antilipemic agent · apolipoprotein E · atherosclerosis · pathophysiology · sensitivity and specificity · Animals · Antihypertensive Agents · Antilipemic Agents · Apolipoproteins E · Atherosclerosis · Disease Models, Animal · Dose-Response Relationship, Drug · Drug Administration Schedule · Dyslipidemias · Humans · Hydroxymethylglutaryl-CoA Reductase Inhibitors · Hypertension · Male · Mice · Mice, Knockout · Mice, Transgenic · Sensitivity and Specificity


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. © 2007 American Heart Association, Inc.