, 2008). With respect to smoking as a risk factor, it has long been acknowledged that the use of combustible tobacco products elevates the likelihood of an individual developing cardiovascular disease (Rosamond et al., 2007). This may be linked to exposure to one (or a combination) of a number of cigarette smoke toxicants which modify the activity and function of cells Small Molecule Compound Library within the cardiovascular
system and initiate pathogenic processes. Cigarette smoke is a complex mixture composed of more than 5,600 chemicals (Perfetti and Rodgman, 2011). Within this unique matrix, several chemicals have been identified as toxicants and are thought to drive disease processes (Hoffman and Hecht, 1990). While attempts have been made to identify
those compounds that have the greatest risk of inducing disease, no single toxicant or group of toxicants has been identified as the inducer of cardiovascular disease processes. Specific smoke constituents have been administered to animal models of cardiovascular disease in order to assess their effects on atherosclerotic lesion development (O’Toole et al., 2009 and Srivastava et al., 2011). However, a single compound behaves much differently in a simple state this website than when it is combined with >5,600 unique compounds with unique properties (e.g., free radicals, antioxidants, toxicants). Moreover, it is further likely that direct interactions with compounds in the complex smoke mixture may have mitigating effects. Since the identity of the compound(s) in cigarette smoke that drive lesion progression remains elusive, an approach that has received considerable attention of late has been the development of potentially reduced-exposure products (PREP). In 2001, the US Institute of Medicine reported that, since smoking-related diseases were dose related, and because epidemiological studies show reduction in the risk of smoking-related diseases following
cessation, it might be possible to reduce smoking-related risks by developing PREPs (Stratton et al., 2001). In this report a framework was proposed for the assessment of the biological effects of cigarettes with modified Tolmetin yields of smoke toxicants. An important component of this approach to product evaluation is the use of in vitro models of smoking-related diseases, including cardiovascular disease. Alongside data from other studies (smoke chemistry evaluation, clinical studies examining biomarkers of both exposure and of biological effect, in vitro and in vivo toxicological studies, in vivo models of disease and epidemiological studies), findings made using in vitro disease models would form part of a weight-of-evidence approach to evaluate and support any proposed change in biological effect. What is lacking from this framework is a detailed insight into not only which models to use but how they would form a part of the overall evaluation framework.