To better understand the impact cigarette smoking has on cardiovascular disease, in vivo and in vitro models have been explored. First, atherosclerosis was assessed in the aorta of apoE knockout mice. ApoE is a gene involved in lipoprotein clearance. Inactivation of the gene results in arterial cholesterol accumulation and the development of atherosclerosis. ApoE -/- mice (+/- atherogenic diet) were exposed nose-only to mainstream cigarette smoke (MCS) (0-0.48 μg/mL wet total particulate matter [WTPM]) and evaluated for CVD using histopathology, virtual histology, lipid chemistry and global genomic approaches. Second, primary cultures of human aortic endothelial cells (HAEC) were exposed acutely or chronically to aqueous extracts of MCS. Global genomic profiling was used to assess the effects of cigarette smoke extract on molecular changes in HEAC.

Atherosclerosis development in the thoracic aorta was enhanced in apoE knockout mice in the presence of both an atherogenic diet and MCS. Gene expression analysis identified several novel and “traditional” cardiovascular gene alterations (GREM1, CXCL1, THBS1, and VCAM1). Acute exposures of HAEC to aqueous MCS extracts resulted in limited numbers of gene expression changes. However, in the HAEC chronic exposure model, several gene expression changes were observed, many of which, were similarly observed in the in vivo model.

When using simple in vitro models to simulate complex disease processes, it is imperative that the endpoints are linked back to human data or a relevant biological model. The HAEC chronic in vitro exposure model shows promising linkages to our in vivo model of atherosclerosis and may further our understanding of the biological relevance of responses in in vitro models.