Integration of data from the in vitro long-term exposure study on human endothelial cells and the in silico analysis: A case of dibutyl phthalate-induced vascular dysfunction

Abstract

General population is exposed to dibutyl phthalate (DBP) through continuous use of various consumer products. DBP exhibits its effects mainly on the endocrine and reproductive system but it can also affect the function of the vasculature; however, the underlying mechanisms behind DBP-induced vascular dysfunction are not fully understood. To infer pathways, molecular functions, biological processes, and human diseases associated with DBP exposure, we integrated the toxicogenomic data obtained from the 4-week-long exposure of human vascular endothelial cells (ECs) to three environmentally relevant concentrations of DBP with the in silico analysis. Nine genes were affected by DBP exposure: six of the integrin family, VCAM1, ICAM1, and MMP2. As shown by the in silico analysis, changes in DBP-affected genes could affect extracellular matrix and binding of molecules and cells to ECs, thereby altering cell adhesion and migration. Several pathways, molecular functions, and biological processes were further identified to provide insight into the DBP-vascular disease relationships and the potential mechanism of action. The top three human disease categories associated with DBP exposure and vascular dysfunction include cardiovascular, cerebrovascular, and immune system diseases. Integration of experimental and in silico approaches may offer better understanding of the potential human health risks associated with DBP exposure.