ST Depression, Arrhythmia, Vagal Dominance, and Reduced Cardiac Micro-RNA in Particulate-Exposed Rats

Abstract

Recently, investigators demonstrated associations between fine particulate matter (PM)-associated metals and adverse health effects. Residual oil fly ash (ROFA), a waste product of fossil fuel combustion from boilers, is rich in the transition metals Fe, Ni, and V, and when released as a fugitive particle, is an important contributor to ambient fine particulate air pollution. We hypothesized that a single-inhalation exposure to transition metal-rich PM will cause concentration-dependent cardiovascular toxicity in spontaneously hypertensive (SH) rats. Rats implanted with telemeters to monitor heart rate and electrocardiogram were exposed once by nose-only inhalation for 4 hours to 3.5 mg/m(3), 1.0 mg/m(3), or 0.45 mg/m(3) of a synthetic PM (dried salt solution), similar in composition to a well-studied ROFA sample consisting of Fe, Ni, and V. Exposure to the highest concentration of PM decreased T-wave amplitude and area, caused ST depression, reduced heart rate (HR), and increased nonconducted P-wave arrhythmias. These changes were accompanied by increased pulmonary inflammation, lung resistance, and vagal tone, as indicated by changes in markers of HR variability (increased root of the mean of squared differences of adjacent RR intervals [RMSSD], low frequency [LF], high frequency [HF], and decreased LF/HF), and attenuated myocardial micro-RNA (RNA segments that suppress translation by targeting messenger RNA) expression. The low and intermediate concentrations of PM had less effect on the inflammatory, HR variability, and micro-RNA endpoints, but still caused significant reductions in HR. In addition, the intermediate concentration caused ST depression and increased QRS area, whereas the low concentration increased the T-wave parameters. Thus, PM-induced cardiac dysfunction is mediated by multiple mechanisms that may be dependent on PM concentration and myocardial vulnerability (this abstract does not reflect the policy of the United States Environmental Protection Agency).

A new cue for torpor induction: charcoal, ash and smoke

“…Importantly, our study identifies a charcoal and ash substrate as a new cue that signals antechinus to enhance torpor use to save energy. In rats and mice, exposure to particulate matter, such as ash, results in reduced heart rate or heart rate variability via vagal regulation and also causes lung inflammation (Swoap et al, 2008;Pham et al, 2009;Farraj et al, 2011). Additionally, as T b regulation involves the hypothalamus (Heller et al, 1977;Seebacher, 2009), a fast adjustment to the thermal physiology of the animal can be made, as the presence of these products of fire will herald a potential reduction in food availability.…”

Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

“…Animal models have shown that chronic exposure to air pollutants can produce significant changes in gene expression patterns (8,15,18,28,44), and in humans changes in transcriptional profiles have been correlated with air pollutant exposure (7,9,10,11,30,34,40,45). Together, these data show that pollutant-induced changes in gene expression levels have biological importance.…”

Molecular biomarkers to assess health risks due to environmental contaminants exposure

“…miRNAs have been assessed in cell lines (125), human primary cell cultures (126)(127)(128), human peripheral blood leukocytes (129), tissues (122,130,131) and different body fluids (123,132,133). The latter surrogate samples have been widely used in oncology studies due to miRNA localization in microparticles and exosomes that confer high stability (123).…”

“…For instance, exposure to residual oil flay ash (ROFA), a fine particle product from oil combustion containing transition metals such as Ni, V and Fe, elicited cardiac dysfunction and altered miRNA expression levels in hypertensive rats (130). The study performed by Bollati, et al (2010), in peripheral blood leukocytes from a population of steel workers exposed to metal-rich particulate matter also identified overexpression of two miRNAs related to oxidative stress and inflammation regulation (miR-222 and miR-21) in exposed individuals.…”