With the development of genetically altered mice, the scientific understanding of disease mechanisms and processes has greatly advanced the field. These understandings would have been considerably delayed using strictly in vitro laboratory assays. For example,

consider the apoE−/− mouse model of atherosclerosis. The apoE−/− mouse lacks apolipoprotein E, a key protein involved in the clearance of LDL including β-very low density lipoproteins (β-VLDL). These mice rapidly develop atherosclerotic plaques that closely resemble those of humans both in location and severity. The durations of experiments and their related costs are considerably decreased compared to many other models of cardiovascular disease. Even in a well described animal model, some limitations are present. In the case of the apoE−/− mouse model, these animals typically

do not develop thrombi seen in humans. Also, initial plaque development occurs at the aortic sinus, an area not particularly of selleck screening library concern in humans. Despite these drawbacks, the apoE−/− mouse model continues to provide valuable information related to the development of cardiovascular disease mechanisms. The Institute of Medicine has clearly stated that as part of a thorough testing strategy “Animal models…can contribute to the… development of a scientific basis for designing and evaluating harm reduction products” (Stratton et al., 2001). The Institute of Medicine also states that “animal models are limited” and recommend the “development of appropriate animal models” Rucaparib cell line to study the pathogenesis of disease. The value of informative and quality animal models of cardiovascular disease is crucial to study the effects of Tanespimycin smoking on disease processes. At the same time, it is also important to emphasise the importance

of the “3Rs”, refinement, reduction and replacement in animal research. The use of in vivo models should ultimately enhance the development and use of in vitro assays to study and assess the effects of cigarette smoke exposure on cardiovascular disease in a complementary framework. Cigarette smoking poses a substantial risk to cardiovascular health, a risk which could potentially be reduced by the production of modified risk tobacco products with altered toxicant yields. Any reduction in risk needs to be substantiated using a framework of pre-clinical and clinical studies designed to characterise the modified risk and a pivotal component of this framework is the use of in vitro models. This was further emphasised with the recent report by the Institute of Medicine (2012) examining the scientific standards for studies on modified risk tobacco products. While our knowledge of how these in vitro models operate is strong, further development is necessary in areas such as cellular metabolic capacity, cell-to-cell interactions, co-culture models, flow-based vs. static models and exposure systems. The use of in silico modelling as a predictive tool is also a potential area for future exploration.