Persistent Organic Pollutants (POPs) Increase Rage Signaling to Promote Downstream Cardiovascular Remodeling
ORCID
Kaplan: https://orcid.org/0000-0002-1992-4145; Stewart: https://orcid.org/0000-0001-8920-8809
MSU Affiliation
College of Arts and Sciences; Department of Biological Sciences; College of Veterinary Medicine; Department of Basic Sciences
Creation Date
2026-03-30
Abstract
Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5-weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6-weeks. At the end of 6-weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE-RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α-smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase-1 and -2 (SOD-1 and SOD-2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling.
Publication Date
10-1-2019
Publication Title
Environmental Toxicology
Publisher
Wiley
First Page
1149
Last Page
1159
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Coole JB, Burr SS, Kay AM, et al. Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling. Environmental Toxicology. 2019;34:1149–1159. https://doi.org/10.1002/tox.22817
