title: miRNA expression profiles and retinal blood vessel calibers are associated with short-term particulate matter air pollution exposure.
abstract: BACKGROUND
  Air pollution, a risk factor for cardiovascular diseases, can exert its effects through the microcirculation. Retinal blood vessel width is considered a marker for microvascular health and is associated with short-term PM10 exposure. microRNAs are key regulators of complex biological processes in cardiovascular health and disease and miRNA expression can be affected by air pollution exposure. Studies investigating the effect of ambient air pollution exposure on miRNA expression in combination with an assessment of the microvasculature do not exist.
  
  
  METHODS
  50 healthy adults (50% women, 23-58 years old) were examined once a month from December 2014 until April 2015 in Flanders (Belgium). Fundus photos and venous blood samples were collected during the study visits. PM10 data were obtained from a nearby monitoring station. Image analysis was used to calculate the width of retinal blood vessels, represented as the Central Retinal Arteriolar/Venular Equivalent (CRAE/CRVE). Total miRNA was isolated from blood and the expression of miR-21, -146a and, -222 were measured using quantitative real-time PCR. Mixed models were used for statistical analysis.
  
  
  RESULTS
  Each short-term increase of 10µg/m(3) PM10 during the 24h preceding the study visit was associated with a 0.58µm decrease (95% CI: -1.16, -0.0005; p=0.056) in CRAE, a 0.99µm increase (95% CI: 0.18, 1.80; p=0.021) in CRVE, a 6.6% decrease (95% CI: -11.07, -2.17; p=0.0038) in miR-21 expression and a 6.7% decrease (95% CI: -10.70, -2.75; p=0.0012) in miR-222 expression. Each 10% increase in miR-21 was associated with a 0.14µm increase (95% CI: 0.0060, 0.24; p=0.046) in CRAE whereas a similar increase in miR-222 expression was associated with a 0.28µm decrease (95% CI: -0.50, -0.062; p=0.016) in CRVE. These associations were also found in exposure windows ranging from 2h to 1 week. Finally, we observed that the association between PM10 exposure and CRAE was mediated by miRNA-21 expression.
  
  
  CONCLUSIONS
  PM10 exposure was associated with retinal arteriolar narrowing and venular widening. PM10 exposure affected miRNAs that are involved in inflammatory and oxidative stress pathways. We suggest that miRNA changes may be relevant to explain the association between PM10 and retinal vessel calibers.
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
authors.forename: Tijs
authors.initials: T
authors.lastname: Louwies
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vuegen
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; Transportation Research Institute, Hasselt University, Hasselt, Belgium.
authors.forename: Luc Int
authors.initials: LI
authors.lastname: Panis
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
authors.forename: Bianca
authors.initials: B
authors.lastname: Cox
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Vrijens
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium; Department of Public Health & Primary Care, Leuven University, Leuven, Belgium.
authors.forename: Tim S
authors.initials: TS
authors.lastname: Nawrot
authors.affiliation: Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium. Electronic address: patrick.deboever@vito.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Boever
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001530:Belgium; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity*; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D035683:MicroRNAs; D052638:Particulate Matter
keywords: Air pollution; Microvascular changes; Retina; miRNA expression