Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling

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.

Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease

“…Similarly, elevated levels of transnonachlor have been linked to clinical manifestations of atherosclerosis, compromised glycemic control, and impaired beta cell function . Exposure to OC mixtures in mice has also shown to be able to intensify oxidative and inflammatory stressors in the heart to overwhelm protective mechanisms allowing for adverse cardiac remodeling …”

“… 53 Exposure to OC mixtures in mice has also shown to be able to intensify oxidative and inflammatory stressors in the heart to overwhelm protective mechanisms allowing for adverse cardiac remodeling. 54 …”

“…53 Exposure to OC mixtures in mice has also shown to be able to intensify oxidative and inflammatory stressors in the heart to overwhelm protective mechanisms allowing for adverse cardiac remodeling. 54 Furthermore, both PCBs and OCPs accumulate in human adipose tissue, 55 affecting its function and fat distribution, and could thereby represent a mechanistic link between adipose tissue inflammation and dysfunction and cardiometabolic diseases. Accumulation of OCs in human adipose tissue has been correlated with adipose tissue macrophage infiltration, adipocyte size, parameters of glucose metabolism, inflammation, and variation in fat distribution.…”

Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage

“…POPs have been related to the development of chronic diseases. Multiple epidemiological studies in different European countries highlighted the strong correlation between the presence of POPs in the circulating system, and the high risk of metabolic and cardiovascular diseases [ 25 , 26 , 27 , 28 , 29 ]. Recently, non-diabetic and diabetic mouse models showed that POPs exposure promotes metabolic syndrome independently of the diet by intensify oxidative and inflammatory stressors, which has for consequence to exacerbate the adverse cardiac remodeling [ 30 ].…”

Determinants of Persistent Organic Pollutants (POPs) Levels in Human Specimens: A Review

“…Data regarding POPs poisoning in humans is generally unavailable since these pollutants tend to cause chronic health effects. POPs presence in any human specimens has been known to cause human health risks, such as type 2 diabetes and gestational diabetes mellitus (21)(22)(23), breast cancer (24)(25), and cardiovascular diseases (26)(27). It is also well known that POPs are considered endocrine-disrupting chemicals (EDCs).…”