Polycyclic aromatic hydrocarbons exposure and arterial stiffness-related plasma miRNAs: A panel study.

The underlying mechanisms between polycyclic aromatic hydrocarbons (PAHs) exposure and arterial stiffness are poorly understood. We carried out a panel study involving three repeated surveys to examine the associations of individual and mixture of PAHs exposure with arterial stiffness-related miRNAs among 123 community adults. In linear mixed-effect (LME) models, we found that urinary 9-hydroxyfluorene (9-OHFlu), 2-hydroxyphenanthrene (2-OHPh), 9-hydroxyphenanthrene (9-OHPh) at lag 0 day were positively linked to miR-146a and/or miR-222. The Bayesian kernel machine regression (BKMR) analyses revealed positive overall associations of PAHs mixture at lag 0 day with miR-146a and miR-222, and urinary 9-OHFlu contributed the most. In addition, an inter-quartile range (IQR) increase in urinary 9-OHFlu at lag 0 day was associated with elevated miR-146a and miR-222 by 0.16 (95% CI: 0.02, 0.30) to 0.34 (95% CI: 0.13, 0.54). Accordingly, exposure to PAHs, especially 9-OHFlu at lag 0 day, was related to elevated arterial stiffness-related plasma miRNAs.

The mediating role of plasma microRNAs in the association of phthalates exposure with arterial stiffness: A panel study.

Phthalates exposure has been reported to be linked with arterial stiffness. However, the biological mechanisms underlying this association remain unclear. We conducted a panel study using 338 paired urine-blood samples by repeated measurements of 123 adults across 3 seasons to assess the potential mediating role of plasma microRNAs (miRNAs) in the association of phthalates exposure with arterial stiffness. We measured 10 urinary phthalate metabolites by gas chromatography-tandem mass spectrometry (GC-MS/MS) and 5 candidate arterial stiffness-related miRNAs (miR-146a, miR-222, miR-125b, miR-126, and miR-21) in plasma by real-time PCR. Arterial stiffness parameters including brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were determined in health examinations during each visit. Linear mixed-effect (LME) models revealed that mono-methyl phthalate (MMP), mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MBP), mono-n-octyl phthalate (MOP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) were significantly associated with one or more of the 5 plasma miRNAs (all PFDR < 0.05). Based on weighted quantile sum (WQS) regression, we found positive associations of phthalate metabolites mixture with miR-146a, miR-125b, and miR-222, and individual MMP and MBP were the major contributors. Additionally, miR-146a was inversely related to ABI. Mediation analysis further indicated that miR-146a mediated 31.6% and 21.3% of the relationships of MMP and MiBP with ABI, respectively. Our findings suggested that certain phthalates exposure was related to plasma miRNAs alterations in a dose-response manner and miR-146a might partly mediate phthalate-associated ABI reduction.

Urinary phthalate metabolites and arterial stiffness: A panel study.

The link between phthalates exposure and arterial stiffness in adults remains unclear. We aimed to investigate the associations of urinary phthalate metabolites with arterial stiffness in a longitudinal panel study involving 3 repeated visits among 127 Chinese adults. Urine samples were collected once a day for 4 consecutive days and 10 urinary phthalate metabolites were measured by gas chromatography-tandem mass spectrometry (GC-MS/MS). Brachial ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were determined using an oscillometric device (BP-203RPEIII; Omron) in physical examinations during each visit. Linear mixed-effect (LME) models with the adaptive Least Absolute Shrinkage and Selection Operator (LASSO) method were applied to assess the associations between urinary phthalate metabolites and arterial stiffness parameters. The odds ratio (OR) for peripheral arterial disease (PAD) was estimated using generalized estimating equations. For ABI, mono-methyl phthalate (MMP) and mono-n-butyl phthalate (MBP) at lag 0 day were selected by the adaptive LASSO, whereas no phthalates were selected for baPWV. After adjusting for potential covariates and other metabolites, we found ABI reduction was associated with one-unit increase of ln-transformed urinary MBP at lag 0 day [ß = 0.013 (SE = 0.006), P = 0.003)]. Stratified analysis revealed that the inverse association was more evident in males (Pinteraction = 0.025). In addition, we observed a borderline risk of PAD in relation to MBP exposure at lag 0 day (P = 0.06). Our data suggested that environmental exposure to MBP may contribute to arterial stiffness, and the effect seems to be sex-specific.