Cigarette smoking (CS) is the main risk factor for the development and progression of a series of diseases, including cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). Suitable animal models play an important role in understanding of smoke-induced pathogenesis. This study examined the development of hallmarks of both COPD and CVD in Apoe-/- mice exposed to either CS or to an aerosol from a candidate modified risk tobacco product, the tobacco heating system (THS2.2) over an 8-month period. In addition to chronic exposure regimes, a comparison of exposure cessation or switching to THS2.2 after 2 months of exposure to CS was performed using a battery of assays (physiological, morphological and molecular). Biological interpretation of various endpoints enables to understand the biological effects of cessation/switching as compared to continuous smoking.