Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction — A population-based prospective cohort study

Bergkvist, Charlotte; Berglund, Marika; Glynn, Anders; Wolk, Alicja; Åkesson, Agneta

doi:10.1016/j.ijcard.2015.01.055

Cited by 45 publications

(21 citation statements)

References 58 publications

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“…Fatty fish is the major contributor to dietary PCB exposure in populations with relatively high fish consumption. We have found that a high dietary intake of PCBs is associated with a significantly increased risk of myocardial infarction and stroke in the SMC and COSM [22][23][24]. Hence, a high degree of exposure to PCBs may explain the observed higher CVD and all-cause mortality risk associated with a high intake of fish, particularly fatty fish.…”

Section: Discussionmentioning

confidence: 85%

Fish consumption and all‐cause mortality in a cohort of Swedish men and women

2016

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Section: Discussionmentioning

confidence: 85%

Fish consumption and all‐cause mortality in a cohort of Swedish men and women

2016

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“…The cardiac RyRisoform, RyR2, is also sensitive to NDL PCBs (Pessah et al, 2009) but whether NDL PCB activity at RyR2 causes cardiac EC-coupling dysfunction requires further elucidation. Such studies may help explain the observed effects of PCB exposure that has been associated with an increase in cardiac physiological dysfunction (Bergkvist et al, 2015). Finally, the RyR and related Ca 2þ signaling proteins have been demonstrated to have roles in diseases ranging from cardiac arrhythmias (Lacampagne et al, 2008) and malignant hypothermia (Robinson et al, 2006) to Alzheimer's disease (Bruno et al, 2012;Stutzmann et al, 2006) and autism spectrum disorder Shelton et al, 2012;Stamou et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

An Extended Structure–Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors

et al. 2016

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Nondioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine-sensitive Ca 2þ channels (RyRs) and this activation has been associated with neurotoxicity in exposed animals. RyR-active congeners follow a distinct structure-activity relationship and a quantitative structure-activity relationship (QSAR) predicts that a large number of PCBs likely activate the receptor, which requires validation. Additionally, previous structural based conclusions have been established using receptor ligand binding assays but the impact of varying PCB structures on ion channel gating behavior is not understood. We used [ 3 H]Ryanodine ([ 3 H]Ry) binding to assess the RyR-activity of 14 previously untested PCB congeners evaluating the predictability of the QSAR. Congeners determined to display widely varying potency were then assayed with single channel voltage clamp analysis to assess direct influences on channel gating kinetics. The RyR-activity of individual PCBs assessed in in vitro assays followed the general pattern predicted by the QSAR but binding and lipid bilayer experiments demonstrated higher potency than predicted. Of the 49 congeners tested to date, tetra-ortho PCB 202 was found to be the most potent RyR-active congener increasing channel open probability at 200 pM. Shifting meta-substitutions to the paraposition resulted in a > 100-fold reduction in potency as seen with PCB 197. Non-ortho PCB 11 was found to lack activity at the receptor supporting a minimum mono-ortho substitution for PCB RyR activity. These findings expand and support previous SAR assessments; where out of the 49 congeners tested to date 42 activate the receptor demonstrating that the RyR is a sensitive and common target of PCBs.

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“…A flow diagram of the literature search and study selection is shown in Figure 1; 18 RCTs (21 publications) and 16 prospective cohort studies (18 publications) [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] were included in the meta-analysis. Studies excluded after full-text review are listed in Supplemental Table 1 (available online at http://www.mayoclinicproceedings.org).…”

Section: Descriptive Study Characteristicsmentioning

confidence: 99%