Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice via TRPA1

Thompson, L. C.; Walsh, Leon; Martin, Brandi L; McGee, John K.; Wood, Charles E.; Kovalcik, Kasey; Pancras, J. Patrick; Haykal-Coates, Najwa; Ledbetter, Allen D.; Davies, David W.; Cascio, Wayne E.; Higuchi, Mark; Hazari, Mehdi S.; Farraj, Aimen K.

doi:10.1093/toxsci/kfy262

Cited by 25 publications

(14 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When applied intermittently with acrolein, PM2.5 activates TRPA1 and leads to cardiac desynchrony in mice. The intermittent application elicits unique effects, which differ from the ones produced by individual exposure [101]. Electrocardiograms show that concentrations 30-fold lower than in highly polluted cities elicit an immediate decrease in heart rate, QRS, QT and Tpe intervals and increase in Pdur.…”

Section: Ambient Particlesmentioning

confidence: 95%

“…The overall effect of DEP is neurogenic inflammation through release of substance P and neurokinin A (mediated by TRPA1 and TRPV1) and through production of cytokines and chemokines (mediated by TRPV1 and TRPM8), and variations in TRPA1 activation promote differences in lung inflammation and injury [33,95,98]. The activation of TRPA1 by DEP is also responsible for cardiac dysfunction, respiratory responses (by increased release of glutamate triggered by the acrolein component) [95,101], reduced asthma control [96] and locomotor hyperactivity [99]. One major issue of the studies on the effect of DEP on TRP channels is that the concentrations used are higher than those found in high polluted areas and the results might not reflect the actual effects elicited by this form of pollution in humans.…”

Section: Diesel Exhaustmentioning

confidence: 99%

“…The composition of ambient particles (AP) varies widely with the region they are collected from and depends on factors such as pollution and natural environment. Nevertheless, they consist of organic carbon, ammonium sulfate, silicon dioxide, and oxides of aluminum, iron, calcium, potassium, magnesium, sodium and titanium [101,103,104]. These compounds can activate TRP channels, being TRPA1 the most susceptible of them, followed by TRPM8, whereas TRPV1 and TRPV4 are activated the least [51].…”

Section: Ambient Particlesmentioning

confidence: 99%

See 2 more Smart Citations

TRP Channels as Cellular Targets of Particulate Matter

Milici

Talavera

2021

IJMS

View full text Add to dashboard Cite

Particulate matter (PM) is constituted by particles with sizes in the nanometer to micrometer scales. PM can be generated from natural sources such as sandstorms and wildfires, and from human activities, including combustion of fuels, manufacturing and construction or specially engineered for applications in biotechnology, food industry, cosmetics, electronics, etc. Due to their small size PM can penetrate biological tissues, interact with cellular components and induce noxious effects such as disruptions of the cytoskeleton and membranes and the generation of reactive oxygen species. Here, we provide an overview on the actions of PM on transient receptor potential (TRP) proteins, a superfamily of cation-permeable channels with crucial roles in cell signaling. Their expression in epithelial cells and sensory innervation and their high sensitivity to chemical, thermal and mechanical stimuli makes TRP channels prime targets in the major entry routes of noxious PM, which may result in respiratory, metabolic and cardiovascular disorders. On the other hand, the interactions between TRP channel and engineered nanoparticles may be used for targeted drug delivery. We emphasize in that much further research is required to fully characterize the mechanisms underlying PM-TRP channel interactions and their relevance for PM toxicology and biomedical applications.

show abstract

Section: Ambient Particlesmentioning

confidence: 95%

Section: Diesel Exhaustmentioning

confidence: 99%

Section: Ambient Particlesmentioning

confidence: 99%

See 1 more Smart Citation

TRP Channels as Cellular Targets of Particulate Matter

Milici

Talavera

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…On the other hand, AITC increased the incidence of arrhythmia in rats, and this effect is inhibited by cholinergic antagonists (Hooper et al, 2016). Furthermore, acrolein, a smoke component, increases the heart rate variability and arrhythmia in mice, and this effect disappears after knocking out the TRPA1 gene or giving TRPA1 inhibitors (Kurhanewicz et al, 2017(Kurhanewicz et al, , 2018Thompson et al, 2019). Continued exposure to air pollution, toxic chemicals, and particulate matter (PM) causes inflammation of the lungs, leading to cough, asthma, chronic obstructive pulmonary disease (COPD), and other diseases.…”

Section: Trpa1 and Arrhythmiamentioning

confidence: 99%

Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases

et al. 2020

View full text Add to dashboard Cite

Cardiovascular disease is one of the chronic conditions with the highest mortality rate in the world. Underlying conditions such as hypertension, metabolic disorders, and habits like smoking are contributors to the manifestation of cardiovascular diseases. The treatment of cardiovascular diseases is inseparable from the development of drugs. Consequently, this has led to many researchers to focus on the search for effective drug targets. The transient receptor potential channel Ankyrin 1 (TRPA1) subtype is a non-selective cation channel, which belongs to the transient receptor potential (TRP) ion channel. Previous studies have shown that members of the TRP family contribute significantly to cardiovascular disease. However, many researchers have not explored the role of TRPA1 as a potential target for the treatment of cardiovascular diseases. Furthermore, recent studies revealed that TRPA1 is commonly expressed in the vascular endothelium. The endothelium is linked to the causes of some cardiovascular diseases, such as atherosclerosis, myocardial fibrosis, heart failure, and arrhythmia. The activation of TRPA1 has a positive effect on atherosclerosis, but it has a negative effect on other cardiovascular diseases such as myocardial fibrosis and heart failure. This review introduces the structural and functional characteristics of TRPA1 and its importance on vascular physiology and common cardiovascular diseases. Moreover, this review summarizes some evidence that TRPA1 is correlated to cardiovascular disease risk factors.

show abstract

“…Acrolein is a volatile, unsaturated aldehyde and a toxic combustion product present in tobacco smoke and fires (Stevens and Maier, 2008). Recent research reported that exposure to acrolein increased heart rate (HR) variability and the incidence of arrhythmias in WT mice, while these consequences were eliminated in TRPA1 −/− mice (Kurhanewicz et al, 2016; Kurhanewicz et al, 2018; Thompson et al, 2019). Moreover, exposure to diesel exhaust (DE) and aconitine increased sympathetic activation in spontaneously hypertensive rats.…”

Section: Role Of the Trpa1 Channel In The Cardiovascular Systemmentioning

confidence: 99%

The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges

Wang

Ye²,

Ye³

et al. 2019

Front. Pharmacol.

View full text Add to dashboard Cite

The transient receptor potential ankyrin 1 (TRPA1) channel is a calcium-permeable nonselective cation channel in the plasma membrane that belongs to the transient receptor potential (TRP) channel superfamily. Recent studies have suggested that the TRPA1 channel plays an essential role in the development and progression of several cardiovascular conditions, such as atherosclerosis, heart failure, myocardial ischemia–reperfusion injury, myocardial fibrosis, arrhythmia, vasodilation, and hypertension. Activation of the TRPA1 channel has a protective effect against the development of atherosclerosis. Furthermore, TRPA1 channel activation elicits peripheral vasodilation and induces a biphasic blood pressure response. However, loss of channel expression or blockade of its activation suppressed heart failure, myocardial ischemia–reperfusion injury, myocardial fibrosis, and arrhythmia. In this paper, we review recent research progress on the TRPA1 channel and discuss its potential role in the cardiovascular system.

show abstract

Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice via TRPA1

Cited by 25 publications

References 61 publications

TRP Channels as Cellular Targets of Particulate Matter

TRP Channels as Cellular Targets of Particulate Matter

Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases

The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges

Contact Info

Product

Resources

About