A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant

Brette, Fabien; Shiels, Holly A.; Galli, Gina L. J.; Cros, Caroline; Incardona, John P.; Scholz, Nathaniel L.; Block, Barbara A.

doi:10.1038/srep41476

Cited by 126 publications

(137 citation statements)

References 56 publications

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“…In addition to the depressive effects on Ca 2+ cycling, Phe was found to affect membrane excitability by prolonging action potential duration (APD) by inhibiting K + efflux from the cardiomyocyte via the rapid delayed rectifier K + ‐current ( I Kr ) (Brette et al . , ), analogous to the original observations in zebrafish embryos (Incardona et al . ).…”

Section: Introductionsupporting

confidence: 82%

“…Consistent with the in vivo whole‐heart effects observed in exposed fishes, these studies demonstrated that complex mixtures of crude oil, or Phe in isolation, altered both cellular Ca 2+ cycling and AP waveform (Brette et al . , ; see Fig. ).…”

Section: Introductionmentioning

confidence: 86%

“…), and a deeper mechanistic understanding of the cardiotoxic pathways followed the 2010 Deepwater Horizon (DWH) blowout (Brette et al . , ). While there are undoubtedly clear differences in air pollutants and aquatic environmental pollution (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Phe; Brette et al . ) on action potential (AP) generation and EC coupling in single isolated myocytes from pelagic fish. Consistent with the in vivo whole‐heart effects observed in exposed fishes, these studies demonstrated that complex mixtures of crude oil, or Phe in isolation, altered both cellular Ca 2+ cycling and AP waveform (Brette et al .…”

Section: Introductionmentioning

confidence: 99%

“…The studies revealed that other single PAHs (naphthalene, fluorene, carbazole, dibenzothiophene and pyrene) did not alter the amplitude or the time course of the intracellular Ca 2+ transient in fish ventricular myocytes (Brette et al . ), and that the potency of the oil‐derived mixture was specifically correlated with the content of Phe (Brette et al . ).…”

Section: Introductionmentioning

confidence: 99%

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Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Marris

Kompella

Miller

et al. 2020

The Journal of Physiology

112

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Air pollution is associated with detrimental effects on human health, including decreased cardiovascular function. However, the causative mechanisms behind these effects have yet to be fully elucidated. Here we review the current epidemiological, clinical and experimental evidence linking pollution with cardiovascular dysfunction. Our focus is on particulate matter (PM) and the associated low molecular weight polycyclic aromatic hydrocarbons (PAHs) as key mediators of cardiotoxicity. We begin by reviewing the growing epidemiological evidence linking air pollution to cardiovascular dysfunction in humans. We next address the pollution‐based cardiotoxic mechanisms first identified in fish following the release of large quantities of PAHs into the marine environment from point oil spills (e.g. Deepwater Horizon). We finish by discussing the current state of mechanistic knowledge linking PM and PAH exposure to mammalian cardiovascular patho‐physiologies such as atherosclerosis, cardiac hypertrophy, arrhythmias, contractile dysfunction and the underlying alterations in gene regulation. Our aim is to show conservation of toxicant pathways and cellular targets across vertebrate hearts to allow a broad framework of the global problem of cardiotoxic pollution to be established. AhR; Aryl hydrocarbon receptor. Dark lines indicate topics discussed in this review. Grey lines indicate topics reviewed elsewhere.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Marris

Kompella

Miller

et al. 2020

The Journal of Physiology

112

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Polycyclic Aromatic Hydrocarbons Phenanthrene and Retene Modify the Action Potential via Multiple Ion Currents in Rainbow Trout Oncorhynchus mykiss Cardiac Myocytes

Vehniäinen

Haverinen

Vornanen

2019

Enviro Toxic and Chemistry

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in aqueous environments. They affect cardiovascular development and function in fishes. The 3‐ring PAH phenanthrene has recently been shown to impair cardiac excitation–contraction coupling by inhibiting Ca2+ and K+ currents in marine warm‐water scombrid fishes. To see if similar events take place in a boreal freshwater fish, we studied whether the PAHs phenanthrene and retene (an alkylated phenanthrene) modify the action potential (AP) via effects on Na+ (INa), Ca2+ (ICaL), or K+ (IKr, IK1) currents in the ventricular myocytes of the rainbow trout (Oncorhynchus mykiss) heart. Electrophysiological characteristics of myocytes were measured using whole‐cell patch clamp. Micromolar concentrations of phenanthrene and retene modified the shape of the ventricular AP, and retene profoundly shortened the AP at low micromolar concentrations. Both PAHs increased INa and reduced ICaL and IKr, but retene was more potent. Neither of the PAHs had an effect on IK1. Our results show that phenanthrene and retene affect cardiac function in rainbow trout by a mechanism that involves multiple cardiac ion channels, and the final outcome of these changes (shortening of AP) is opposite to that observed in scombrid fishes (prolongation of AP). The results also show that retene and aryl hydrocarbon receptor (AhR) agonist have an additional mechanism of toxicity besides the previously known AhR‐mediated, transcription‐dependent one. Environ Toxicol Chem 2019;38:2145–2153. © 2019 SETAC.

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Effects of Phenanthrene Exposure on Cholesterol Homeostasis and Cardiotoxicity in Zebrafish Embryos

McGruer

Tanabe

Vliet

et al. 2021

Enviro Toxic and Chemistry

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Polycyclic aromatic hydrocarbons (PAHs) are pervasive pollutants in aquatic ecosystems, and developing fish embryos are especially sensitive to PAH exposure. Exposure to crude oil or phenanthrene (a reference PAH found in oil) produces an array of gross morphological abnormalities in developing fish embryos, including cardiotoxicity. Recently, studies utilizing transcriptomic analyses in several oil-exposed fish embryos found significant changes in the abundance of transcripts involved in cholesterol biosynthesis. Given the vital role of cholesterol availability in embryonic heart development, we hypothesized that cholesterol dysregulation in early development contributes to phenanthrene-induced cardiotoxicity. We exposed zebrafish embryos to 12 or 15 µM phenanthrene from 6 to 72 h post fertilization (hpf) and demonstrated that, in conjunction with pericardial edema and bradycardia, several genes (fdft1 and hmgcra) in the cholesterol biosynthetic pathway were significantly altered. When embryos were pretreated with a cholesterol solution from 6 to 24 hpf followed by exposure to phenanthrene from 24 to 48 hpf, the effects of phenanthrene on heart rate were partially mitigated. Despite changes in gene expression, whole-mount in situ staining of cholesterol was not significantly affected in embryos exposed to phenanthrene ranging in stage from 24 to 72 hpf. However, the 2-dimensional yolk area was significantly increased with phenanthrene exposure at 72 hpf, suggesting that lipid transport from the yolk to the developing embryo was impaired.

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A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant

Cited by 126 publications

References 56 publications

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Polyaromatic hydrocarbons in pollution: a heart‐breaking matter

Polycyclic Aromatic Hydrocarbons Phenanthrene and Retene Modify the Action Potential via Multiple Ion Currents in Rainbow Trout Oncorhynchus mykiss Cardiac Myocytes

Effects of Phenanthrene Exposure on Cholesterol Homeostasis and Cardiotoxicity in Zebrafish Embryos

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