Association between Urinary Phthalate Metabolites and Markers of Endothelial Dysfunction in Adolescents and Young Adults

Abstract

Endothelial function is crucial in the pathogenesis of circulatory and cardiovascular toxicity; epidemiologic research investigating the association between phthalate exposure and endothelial dysfunction remains limited. We examined the associations between exposures to specific phthalates (di-2-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP) and circulating endothelial and platelet microparticles (EMPs and PMPs) in adolescents and young adults. Of the 697 participants recruited, anthropometric measurements and health-related behaviors relevant to cardiovascular risks were collected and assessed. Urine and serum were collected and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow cytometry. Multiple linear regression indicated that increases in urinary concentrations of ΣDEHP and MnBP (mono-n-butyl phthalate), across quartiles, were positively associated with serum EMPs level (p for trend <0.001 and <0.001; β = 0.798 and 0.007; standard error = 0.189 and 0.001, respectively). Moreover, female and overweight subjects had higher MnBP, and males were more vulnerable to DnBP exposure compared to females. In conclusion, our results demonstrate a dose-response relationship between exposures to phthalates (ΣDEHP and MnBP) and microparticle formation (EMPs and PMPs) in adolescents and young adults. The findings indicate that exposures to phthalates of both low and high-molecular weight are positively associated with microparticle production, and might contribute to endothelial dysfunction; such damage might manifest in the form of atherosclerotic-related vascular diseases. Future in vivo and in vitro studies are warranted to elucidate whether a causal relationship exists between phthalate exposure and EMPs and PMPs.

Association Between Levels of Urine Di-(2-ethylhexyl)phthalate Exposure, a Potentially Harmful and Invisible Chemical, and Heart Rate Variability in Young Adults

“…Increased carotid intima-media thickness was associated with decreased HRV in previous studies [42,43]. Our previous studies showed that urinary phthalate metabolites were associated with endothelial dysfunction, insulin resistance and increased carotid intima-media thickness [12,13,44]. Thus, exposure to DEHP may mediate impaired HRV through these mechanisms.…”

Association between Levels of Urine Di-(2-ethylhexyl)phthalate Metabolites and Heart Rate Variability in Young Adults

“…Increased carotid intima-media thickness was associated with decreased HRV in previous studies [42,43]. Our previous studies showed that urinary phthalate metabolites were associated with endothelial dysfunction, insulin resistance, and increased carotid intima-media thickness [13,14,44]. Thus, exposure to DEHP may mediate impaired HRV through these mechanisms.…”

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust

“…Exogenous and endogenous metabolites with its downstream oxidative stress have been recognized as the common underlying cellular mechanism for the development of endothelial dysfunction among many risk factors for atherosclerosis [ 34 , 35 ]. In this study, primary DNA damage detected in peripheral blood using alkaline comet assay could result from the oxidative stress and reactive cyto/geno-toxic metabolites in circulation.…”