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Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats
Citation:
Upadhyay, S., T. Stoeger, L. George, M. Schladweiler, U. Kodavanti, K. Ganguly, AND H. Schulz. Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats. Particle and Fibre Toxicology. BioMed Central Ltd, London, Uk, 11(1):36, (2014).
Impact/Purpose:
Ultrafine particles have been linked to adverse cardiovascular health effects. This study shows that ultrafine carbon particles induced pulmonary and systemic inflammation in aged hypertensive rats are associated with oxidative stress, endothelial dysfunction and disturbed coagulatory hemostasis. Ultrafine carbon particles also increase BP and HR in both, adult and aged hypertensive rats but the inflammatory response associated with the disturbed coagulatory hemostasis is detected only in aged rats. This study provides further evidence for potential molecular mechanisms explaining the increased risk of particle mediated cardiac health effects in the elderly.
Description:
Background: Previous studies provided compelling evidences for particulate matter (PM) associated cardiovascular health effects. Elderly individuals, particularly those with preexisting conditions like hypertension are regarded to be vulnerable. Experimental data are warranted to reveal the molecular pathomechanism of PM related cardiovascular impairments among aged/predisposed individuals. Thus we investigated the cardiovascular effects of ultrafine carbon particles (UfCP) on aged (12-13 months) spontaneously hypertensive rats (SHRs) and compared the findings to our pervious study on adult SHRs (6-7 months) to identify age related predisposition events.Methods: Aged SHRs were inhalation exposed to UfCP for 24h (~180µg/m3) followed by radio-telemetric assessment for blood pressure (BP) and heart rate (HR). Bronchoalveolar lavage (BAL) fluid cell differentials, interleukin 6 (IL-6) and other proinflammatory cytokines; serum C-reactive protein (CRP) and haptoglobin (HPT); and plasma fibrinogen were measured for assessing pulmonary and systemic inflammation. Transcript levels of hemeoxygenase 1 (HO-1), endothelin 1 (ET1), endothelin receptors A,B (ETA, ETB), tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1) were measured in the lung and heart to assess oxidative stress, endothelial dysfunction and coagulation cascade. Result: UfCP exposed aged SHRs exhibited increased BP (4.4%) and HR (6.3%) on 1st recovery day paralleled by a 58% increase of neutrophils and 25% increase of IL-6 in the BAL fluid. Simultaneously higher CRP, HPT and fibrinogen levels in exposed SHRs indicate systemic inflammation. HO-1, ET1, ET-A, ET-B, TF and PAI-1 were induced by 1.5-2.0 fold in lungs of aged SHRs on 1st recovery day. However, in UfCP exposed adult SHRs these markers were up-regulated (2.5-6 fold) on 3rd recovery day in lung without detectable pulmonary/systemic inflammation.Conclusions: The UfCP induced pulmonary and systemic inflammation in aged SHRs is associated with oxidative stress, endothelial dysfunction and disturbed coagulatory hemostasis. UfCP exposure increased BP and HR in both, adult and aged SHRs rats but the inflammatory response associated with the disturbed coagulatory hemostasis was detected only in aged SHRs. Our study provides further evidence for potential molecular mechanisms explaining the increased risk of particle mediated cardiac health effects in the elderly.