Cardiovascular and inflammatory effects of intratracheally instilled ambient dust from Augsburg, Germany, in spontaneously hypertensive rats (SHRs)

Abstract

RationaleSeveral epidemiological studies associated exposure to increased levels of particulate matter in Augsburg, Germany with cardiovascular mortality and morbidity. To elucidate the mechanisms of cardiovascular impairments we investigated the cardiopulmonary responses in spontaneously hypertensive rats (SHR), a model for human cardiovascular diseases, following intratracheal instillation of dust samples from Augsburg.Methods250 μg, 500 μg and 1000 μg of fine ambient particles (aerodynamic diameter <2.5 μm, PM2.5-AB) collected from an urban background site in Augsburg during September and October 2006 (PM2.5 18.2 μg/m3, 10,802 particles/cm3) were instilled in 12 months old SHRs to assess the inflammatory response in bronchoalveolar lavage fluid (BALF), blood, lung and heart tissues 1 and 3 days post instillation. Radio-telemetric analysis was performed to investigate the cardiovascular responses following instillation of particles at the highest dosage based on the inflammatory response observed.ResultsExposure to 1000 μg of PM2.5-AB was associated with a delayed increase in delta mean blood pressure (ΔmBP) during 2nd-4th day after instillation (10.0 ± 4.0 vs. -3.9 ± 2.6 mmHg) and reduced heart rate (HR) on the 3rd day post instillation (325.1 ± 8.8 vs. 348.9 ± 12.5 bpm). BALF cell differential and inflammatory markers (osteopontin, interleukin-6, C-reactive protein, and macrophage inflammatory protein-2) from pulmonary and systemic level were significantly induced, mostly in a dose-dependent way. Protein analysis of various markers indicate that PM2.5-AB instillation results in an activation of endothelin system (endothelin1), renin-angiotensin system (angiotensin converting enzyme) and also coagulation system (tissue factor, plasminogen activator inhibitor-1) in pulmonary and cardiac tissues during the same time period when alternation in ΔmBP and HR have been detected.ConclusionsOur data suggests that high concentrations of PM2.5-AB exposure triggers low grade PM mediated inflammatory effects in the lungs but disturbs vascular homeostasis in pulmonary tissues and on a systemic level by affecting the renin angiotensin system, the endothelin system and the coagulation cascade. These findings are indicative for promotion of endothelial dysfunction, atherosclerotic lesions, and thrombogeneis and, thus, provide plausible evidence that susceptible-predisposed individuals may develop acute cardiac events like myocardial infarction when repeatedly exposed to high pollution episodes as observed in epidemiological studies in Augsburg, Germany.

Comorbidity of respiratory and cardiovascular diseases among the elderly residing close to mine dumps in South Africa: A cross-sectional study.

“…[35] The cardiovascular and respiratory systems are vulnerable to occupational exposures owing to direct contact with the ambient environment and inhalation of toxic substances. [36,37] Occupational exposure to dust or chemicals was significantly associated with cardiovascular and respiratory diseases. The findings of this study are in agreement with other research in this respect.…”

Manufactured and airborne nanoparticle cardiopulmonary interactions: a review of mechanisms and the possible contribution of mast cells

“…Increases in acute phase response proteins have been associated with metabolic syndrome and the eventual development of diabetes and cardiovascular disease (Saiki et al 2011, Wellen, Hotamisligil 2005, Venteclef et al 2011). The release of acute phase response proteins such as C-reactive protein, fibrinogen, and Factor VII from the liver into circulation also promote a prothrombotic state and are recognized as risk factors for myocardial infarction (Donaldson et al 2001, Upadhyay et al 2010, Wilhelmsen et al 1984, Moyssakis et al 2010). Specifically C-reactive protein is increased following particulate exposure and has been shown to correlate with the development of atherosclerosis and to induce coagulation (Donaldson et al 2001).…”

Effect of particulate matter air pollution on C-reactive protein: a review of epidemiologic studies

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