Lead exposure increases blood pressure by increasing angiotensinogen expression

J Environ Sci Health A Tox Hazard Subst Environ Eng. 2016;51(5):434-9. doi: 10.1080/10934529.2015.1120537. Epub 2016 Jan 28.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensinogen / drug effects*
  • Angiotensinogen / genetics
  • Blood Pressure / drug effects*
  • Case-Control Studies
  • China
  • Environmental Exposure / adverse effects*
  • Female
  • Gene Expression Regulation / drug effects*
  • Genotype
  • HEK293 Cells / drug effects*
  • Haplotypes
  • Humans
  • Hypertension / etiology*
  • Lead / adverse effects*
  • Male
  • Mutagens / adverse effects
  • Polymorphism, Single Nucleotide

Substances

  • Mutagens
  • Angiotensinogen
  • Lead