12 August 2008

SCIENCE: Vascular Effects of Ambient Pollutant Particles and Metals

Article in Current Vascular Pharmacology, (2006) 4, 199-203 by Yuh-Chin T. Huang and Andrew J. Ghio of National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, USA and Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.


Exposure to ambient pollutant particle (APP) is associated with increased cardiovascular morbidity and mortality. Recent evidence indicates that APP-induced vasoconstriction may be an important mechanism. APP constricts systemic arteries and increases blood pressure in human. APP decreases the diameter of pulmonary arterioles in animals. Intratracheal instillation of APP increases pulmonary artery resistance in isolated buffer-perfused lungs, and APP constricts isolated arterial rings. APP-induced vasoconstriction may be secondary to the release of inflammatory mediators from lung cells, which then activate vascular endothelial and smooth muscle cells. The vasoconstriction may also be caused by alterations in autonomic nervous system balance. Some soluble metals (e.g., vanadium) can produce acute vasoconstriction in in vitro and in vivo systems, and contribute to the systemic health effects of APP since they can more easily permeate the alveolar-capillary membrane than the whole particle. Both APP and its associated metals have been shown to enhance the release of endothelin 1 and reactive oxygen species, activate epithelial growth factor receptor and mitogenactivated protein kinases, and inhibit nitric oxide vasodilator activity. The vasoactive properties of APP and metals raised the possibility that patients with vascular diseases may be more susceptible to APP-induced adverse health effects, and that people who are regularly exposed to high amount of metals, e.g., vanadium contained in certain dietary and musclebuilding regimens or in the air of boiler making plants, may have increased risk for vascular diseases. Understanding how metals induce vasoconstriction may lead to the development of novel vasodilator therapies for vascular diseases.


... The present review will focus on how ambient pollutant particle (APP) and its metal constituents affect vascular function. ...


APP is a complex mixture of solid and liquid particles suspended in air. APP varies in size and chemical composition depending on the source and age as well as the surrounding gases. APP can come from anthropogenic (e.g., combustion of fossil fuels), or natural (e.g., soil resuspension) sources with secondary modification by physicochemical reactions between gas and particles in the atmosphere [3]. Consequently APP contains multiple chemical constituents, including metals in the forms of oxides and salts, soluble salts (e.g., ammonium nitrate and sulfates), and organic materials (e.g., elemental carbon and hydrocarbon compounds) [4]. The specific composition and relative abundance of these constituents in APP depend on the sources and thus can vary from place to place. For example, APP from fossil fuel combustion emissions (e.g., oil fly ash) contains large amount of soluble transition metal in additional to a relatively inert carbonaceous matrix. This is in contrast to APP derived from soil (e.g., Mount St. Helen dust) which has almost no transition metals [5].

Over the last decade, a growing body of epidemiological and clinical evidence has raised the possibility of the potentially deleterious effects of ambient pollutant particles on cardiovascular health. Exposure to APP has consistently been associated with increased hospitalization and mortality due to cardiovascular diseases [2,6,7]. It is estimated that the daily cardiopulmonary mortality in the short term increased by 0.3% for each 10-µm/m3 increase in PM10 (particulate matter [PM] <>.

The causes for the short term cardiovascular morbidity and mortality have been investigated. In Sweden, workers with exposure to products from non-vehicular combustion processes had increased risk of myocardial infarction [11]. In Helsinki, Finland, APP was associated with increased risk for hospital admission for transient myocardial ischemic attacks [12]. Elevated concentrations of PM2.5 were associated with a transient risk of developing acute myocardial infarction within hours after exposure [13]. Exposure to PM has also been associated with the development of cerebrovascular disorders [14]. The pathophysiological mechanisms for the increased cardiovascular morbidity and mortality have been proposed, including increases in heart rate and blood pressure [15], fibrinogen [16,17] and blood coagulation factors; decreased heart rate variability [18]; release of inflammatory mediators [19,20]; and endothelial injury/dysfunction and arterial vasoconstriction [21,22]. …


Studies on the cardiovascular adverse effects of APP have had tremendous public health impact. The effects of APP-associated metals on vascular reactivity provide a biologically plausible mechanism for the adverse cardiovascular effects associated with APP. These effects are likely more detrimental in patients with compromised cardiovascular conditions, including congestive heart failure, coronary artery disease and vascular disease (e.g., in diabetes). In addition, the vascular effects of exogenous metals also raise the concerns that people who regularly consume certain weight-reduction and muscle building supplements that contain high amount of vanadyl sulfate (e.g., Satieté®) may be at risk for developing cardiovascular diseases. Future research will be needed to determine the metabolic fate of these environmental metals in the cell and how cellular defense mechanisms are activated to combat the toxicity induced by these metals. Understanding how metals induce vascular changes may lead to development of novel therapy for vascular diseases.

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