Lead exposure increases blood pressure by increasing angiotensinogen expression

ABSTRACT

Lead exposure can induce increased blood pressure. Several mechanisms have been proposed to explain lead-induced hypertension. Changes in angiotensinogen (AGT) expression levels or gene variants may also influence blood pressure. In this study, we hypothesized that AGT expression levels or gene variants contribute to lead-induced hypertension. A preliminary HEK293 cell model experiment was performed to analyze the association between AGT expression and lead exposure. In a population-based study, serum AGT level was measured in both lead-exposed and control populations. To further detect the influence of AGT gene single nucleotide polymorphisms (SNPs) in lead-induced hypertension, two SNPs (rs699 and rs4762) were genotyped in a case-control study including 219 lead-exposed subjects and 393 controls. Lead exposure caused an increase in AGT expression level in HEK 293 cell models (P < 0.001) compared to lead-free cells, and individuals exposed to lead had higher systolic and diastolic blood pressure (P < 0.001). Lead-exposed individuals had higher serum AGT levels compared to controls (P < 0.001). However, no association was found between AGT gene SNPs (rs699 and rs4762) and lead exposure. Nevertheless, the change in AGT expression level may play an important role in the development of lead-induced hypertension.

Keywords:

• Angiotensinogen (AGT)
• hypertension
• lead exposure
• polymorphism

Acknowledgments

Authors Jiandong Jiao and Miaomiao Wang contributed equally to this work.

Funding

This work was supported by Projects for Medical Scientific Research Foundation, Department of Health, Jiangsu Province [grant number H201246]; Nature Science Funds of Jiangsu Province [grant number BK20130112]; and National Natural Science Foundation of China [grant number 81302409].