title: Preclinical mouse models and methods for the discovery of the causes and treatments of atherosclerosis.
abstract: BACKGROUND
  Atherosclerosis is the leading cause of death in the Western world. Despite huge advances in understanding its pathophysiological mechanisms, current treatment is mostly based on 'traditional' risk factors. The introduction of statins more than 20 years ago reduced morbidity and mortality of atherosclerosis by 30%, leaving a residual cardiovascular risk. Therefore, efforts continue toward the development of novel therapies that can be added to established treatments. Besides targeting dyslipidemia, recent focus has been put on preventing or resolving inflammatory processes involved in atherosclerosis.
  
  
  METHODS
  The article discusses therapeutic and diagnostic targets in atherosclerosis and how they can be discovered and studied in preclinical animal models. The roles of immune cells, specifically macrophages and monocytes, in plaque inflammation are discussed. The article also describes current preclinical models of atherosclerosis, specifically the mouse, study designs (for progression and regression studies), basic and advanced methods of analysis of atherosclerotic lesions, and discusses the challenges of translating the findings to humans.
  
  
  CONCLUSIONS
  Advances in genomics, proteomics, lipidomics and the development of high-throughput screening techniques help to improve our understanding of atherosclerosis disease mechanisms immensely and facilitate the discovery of new diagnostic and therapeutic targets. Preclinical studies in animals are still indispensable to uncover pathways involved in atherosclerotic disease and to evaluate novel drug targets. The translation of these targets, however, from animal studies to humans remains challenging. There is a strong need for novel biomarkers that can be used to prove the concept of a new target in humans.
authors.affiliation: NYU School of Medicine, Division of Cardiology, Department of Medicine, NY 10016, USA.
authors.forename: Bernd
authors.initials: B
authors.lastname: Hewing
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D012307:Risk Factors; D013045:Species Specificity; D057170:Translational Research, Biomedical / Q000379:methods