Acute and chronic vascular effects of inhaled crotonaldehyde in mice: Role of TRPA1

Lynch, Jordan; Jin, Lexiao; Richardson, Andre; Jagatheesan, Ganapathy; Lorkiewicz, Pawel; Xie, Zhengzhi; Theis, Whitney S.; Shirk, Gregg; Malovichko, Marina V; Bhatnagar, Aruni; Srivastava, Sanjay; Conklin, Daniel J.

doi:10.1016/j.taap.2020.115120

Cited by 21 publications

(13 citation statements)

References 54 publications

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“…Both naïve male mice and male and female mice exposed to either toxicants or filtered air were euthanized, and the mid‐thoracic aorta was isolated and placed into cold (4℃) physiological salt solution (PSS). Thoracic aorta rings (2–4 mm length) were carefully cleaned (without and with PVAT intact) and prepared for isometric myography as described (Lynch et al, 2020 ). Rat aortas were isolated, cleaned and treated similarly as for murine aorta.…”

Section: Methodsmentioning

confidence: 99%

“…One approach to evaluate ED is to measure biomarkers in the blood, such as the levels of soluble adhesion molecules, microparticles, endothelial progenitor cells, etc. (Leite et al, 2020 ; Lynch et al, 2020 ; O'Toole et al, 2010 ). A more direct method is to measure the changes in conduit artery diameter by ultrasound following induction of flow‐mediated dilation (FMD) in humans (Celermajer, 1985 ; Celermajer et al, 1996 ) and animals in vivo (Heiss et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

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A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”

Jin

Conklin

2021

Physiological Reports

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Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Many CVDs begin with endothelium dysfunction (ED), including hypertension, thrombosis, and atherosclerosis. Our assay evaluated ED in isolated murine aorta by quantifying phenylephrine‐induced contractions (PE) in the presence of L‐NAME, which blocked acetylcholine‐induced relaxation (ACh %; >99%). The “L‐NAME PE Contraction Ratio” (PECR) was defined as: “PE Tension post‐L‐NAME” divided by “PE Tension pre‐L‐NAME.” We hypothesized that our novel PE Contraction Ratio would strongly correlate with alterations in endothelium function. Validation 1: PECR and ACh % values of naïve aortas were strongly and positively correlated (PECR vs. ACh %, r2 = 0.91, n = 7). Validation 2: Retrospective analyses of published aortic PECR and ACh % data of female mice exposed to filtered air, propylene glycol:vegetable glycerin (PG:VG), formaldehyde (FA), or acetaldehyde (AA) for 4d showed that the PECR in air‐exposed mice (PECR = 1.43 ± 0.05, n = 16) correlated positively with the ACh % (r2 = 0.40) as seen in naïve aortas. Similarly, PECR values were significantly decreased in aortas with ED yet retained positive regression coefficients with ACh % (PG:VG r2 = 0.54; FA r2 = 0.55). Unlike other toxicants, inhaled AA significantly increased both PECR and ACh % values yet diminished their correlation (r2 = 0.09). Validation 3: To assess species‐specific dependence, we tested PECR in rat aorta, and found PECR correlated with ACh % relaxation albeit less well in this aged and dyslipidemic model. Because the PECR reflects NOS function directly, it is a robust measure of both ED and vascular dysfunction. Therefore, it is a complementary index of existing tests of ED that also provides insight into mechanisms of vascular toxicity.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”

Jin

Conklin

2021

Physiological Reports

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“…16 Moreover, longitudinal time-series studies have shown that ambient VOCs, such as alkenes and alkynes, are associated with increased heart failure emergency hospitalizations, 19 as well as overall cardiovascular hospitalizations, 20 and that occupational exposure to VOC such as styrene increases the relative risk of death from ischemic heart disease. 21 The biological plausibility that VOCs can induce cardiovascular injury and exacerbate CVD is extensively supported by a range of animal studies showing that exposures to benzene, acrolein, and formaldehyde, can lead to changes in blood pressure regulation, [22][23][24] depletion of circulating stem cells, 25 insulin resistance, 26 and platelet activation. 27 Exposure to these VOCs also induces systemic dyslipidemia, lipoprotein modification, 28 dilated cardiomyopathy; 29 and lead to the acceleration of atherogenesis 30 and exacerbation of myocardial ischemic injury.…”

Section: Introductionmentioning

confidence: 99%

“…The biological plausibility that VOCs can induce cardiovascular injury and exacerbate CVD is extensively supported by a range of animal studies showing that exposures to benzene, acrolein, and formaldehyde, can lead to changes in blood pressure regulation (Awe et al, 2006;Jin et al, 2019;Lynch et al, 2020), depletion of circulating stem cells (Conklin et al, 2017), insulin resistance (Abplanalp et al, 2019), and platelet activation (Sithu et al, 2010). Exposure to these VOCs also induces systemic dyslipidemia, lipoprotein modification (Conklin et al, 2010), dilated cardiomyopathy (Ismahil et al, 2011); and lead to the acceleration of atherogenesis (Srivastava et al, 2011) and exacerbation of myocardial ischemic injury (Wang et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Environmental Exposure to Volatile Organic Compounds is Associated with Endothelial Injury

Riggs

Malovichko

Gao

et al. 2021

Preprint

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Objective: Volatile organic compounds (VOCs) are airborne toxicants abundant in outdoor and indoor air. High levels of VOCs are also present at various Superfund and other hazardous waste sites; however, little is known about the cardiovascular effects of VOCs. We hypothesized that ambient exposure to VOCs exacerbate cardiovascular disease (CVD) risk by depleting circulating angiogenic cells (CACs). Approach and Results: In this cross-sectional study, we recruited 375 non-smokers with low-to-high CVD risk and measured 15 subpopulations of CACs by flow cytometry and 16 urinary metabolites of 12 VOCs by LC/MS/MS. Associations between CAC and VOC metabolite levels were examined using generalized linear models. Our data show that VOC exposure varied by sex, age, and race. In single pollutant models, metabolites of xylene, benzene, and 1,3-butadiene were negatively associated with CAC levels. The metabolite of acrylonitrile was negatively associated with CD45dim/CD146+/CD34+/AC133+ cells and CD45+/CD146+/AC133+, and the toluene metabolite with AC133+ cells. Multipollutant models showed a negative association with metabolites of ethylbenzene/styrene, benzene, and xylene with CD45dim/CD146+/CD34+ cells, independent of other VOC metabolite levels. Cumulative VOC risk score showed a strong negative association with CD45dim/CD146+/CD34+ cells, suggesting that total VOC exposure has a cumulative effect on pro-angiogenic cells. Dose-response relationship showed an increase in CAC levels at low, but depletion at higher levels of VOC exposure. Sex and race, hypertension, and diabetes significantly modified VOC associated CAC depletion. Conclusion: Low-level ambient exposure to VOCs is associated with CAC depletion, which could compromise endothelial repair and angiogenesis, and exacerbate CVD risk.

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“…Population-based studies show that atherosclerosis, the underlying cause of most of myocardial infarction and stroke, is exacerbated by exposure to environmental pollution (4, 5). Studies in experimental animals show that exposure to environmental chemicals such as acrolein augments myocardial ischemic injury (6) and induces dilated cardiomyopathy (7); crotonanaldehyde causes hypotension (8); and acrolein, 1,3-butadiene, and arsenic exacerbate atherosclerosis (9–11). However, little is known about the effect of industrial chemicals on cardiovascular health and injury.…”

Section: Introductionmentioning

confidence: 99%

Effect of Vinyl Chloride Exposure on Cardiometabolic Toxicity

Zelko

Taylor

Das

et al. 2021

Preprint

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Vinyl chloride is an organochlorine mainly used to manufacture its polymer polyvinyl chloride, which is extensively used in the manufacturing of consumer products. Recent studies suggest that chronic low dose vinyl chloride exposure affects glucose homeostasis in high fat diet-fed mice. Our data suggest that even in the absence of high fat diet, exposure to vinyl chloride (0.8 ppm, 6h/day, 5day/week, for 12 weeks) induces glucose intolerance (1.0 g/kg, i.p) in male C57BL/6 mice. This was accompanied with the depletion of hepatic glutathione and a modest increase in lung interstitial macrophages. Vinyl chloride exposure did not affect the levels of circulating immune cells, endothelial progenitor cells, platelet-immune cell aggregates, and cytokines and chemokines. The acute challenge of vinyl chloride-exposed mice with LPS did not affect lung immune cell composition or plasma IL-6. To examine the effect of vinyl chloride exposure on vascular inflammation and atherosclerosis, LDL receptor-KO mice on C57BL/6 background maintained on western diet were exposed to vinyl chloride for 12 weeks (0.8 ppm, 6h/day, 5day/week). Unlike the WT C57BL/6 mice, vinyl chloride exposure did not affect glucose tolerance in the LDL receptor-KO mice. Plasma cytokines, lesion area in the aortic valve, and markers of lesional inflammation in vinyl chloride-exposed LDL receptor-KO mice were comparable with the air-exposed controls. Collectively, despite impaired glucose tolerance and modest pulmonary inflammation, chronic low dose vinyl chloride exposure does not affect surrogate markers of cardiovascular injury, LPS-induced acute inflammation in C57BL/6 mice, and chronic inflammation and atherosclerosis in the LDL receptor-KO mice.

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Acute and chronic vascular effects of inhaled crotonaldehyde in mice: Role of TRPA1

Cited by 21 publications

References 54 publications

A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”

A novel evaluation of endothelial dysfunction ex vivo: “Teaching an Old Drug a New Trick”

Environmental Exposure to Volatile Organic Compounds is Associated with Endothelial Injury

Effect of Vinyl Chloride Exposure on Cardiometabolic Toxicity

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