In silico toxicogenomic data-mining to unraveling the influence of lead and cadmium co-exposure on molecular mechanisms involved in the development and progression of Hypertension

Abstract Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are of public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposures to lead and cadmium have been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the molecular mechanisms using an in silico toxicogenomic approach. The set of genes affected by both metals were identified using the Comparative Toxicogenomics Database (CTD) while HYP targets were retrieved from the GeneCards database. The shared genes between the metals and the disease were identified and subjected to further analyses. The results of our analyses revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of findings on the roles played by lead and cadmium co-exposure in inducing HYP.