title: Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats.
abstract: BACKGROUND
  Studies provide 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 with our pervious study on adult SHRs (6-7 months) to identify age related predisposition events in cardiovascular compromised elderly individuals.
  
  
  METHODS
  Aged SHRs were inhalation exposed to UfCP for 24 h (~180 μg/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. Transcript levels of hemeoxygenase 1 (HO-1), endothelin 1 (ET1), endothelin receptors A, B (ETA, ETB), tissue factor (TF), and plasminogen activator inhibitor-1 (PAI-1) were measured in the lung and heart to assess oxidative stress, endothelial dysfunction and coagulation cascade.
  
  
  RESULTS
  UfCP exposed aged SHRs exhibited increased BP (4.4%) and HR (6.3%) on 1(st) 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 folds in lungs of aged SHRs on 1(st) recovery day. However, in UfCP exposed adult SHRs these markers were up-regulated (2.5-6 fold) on 3(rd) 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 aged SHRs rats which was associated with lung inflammation, and increased expression of inflammatory, vasoconstriction and coagulation markers as well as systemic changes in biomarkers of thrombosis in aged SHRs. Our study provides further evidence for potential molecular mechanisms explaining the increased risk of particle mediated cardiac health effects in cardiovascular compromised elderly individuals.
authors.affiliation: Institute of Lung Biology and Disease, Comprehensive Pneumology Center Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany. swapnaupadhyay@gmail.com.|Department of Biotechnology, Indian Institute of Technology, Madras, Chennai, 600036, India. swapnaupadhyay@gmail.com.
authors.forename: Swapna
authors.initials: S
authors.lastname: Upadhyay
authors.affiliation: Institute of Lung Biology and Disease, Comprehensive Pneumology Center Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany. tobias.stoeger@helmholtz-muenchen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Stoeger
authors.affiliation: SRM Research Institute, SRM University, Chennai, 603203, India. leema.g@res.srmuniv.ac.in.
authors.forename: Leema
authors.initials: L
authors.lastname: George
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, NC, 27711, USA. Schladweiler.Mette@epamail.epa.gov.
authors.forename: Mette C
authors.initials: MC
authors.lastname: Schladweiler
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, NC, 27711, USA. kodavanti.urmila@epa.gov.
authors.forename: Urmila
authors.initials: U
authors.lastname: Kodavanti
authors.affiliation: Institute of Lung Biology and Disease, Comprehensive Pneumology Center Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany. koustav.g@res.srmuniv.ac.in.|SRM Research Institute, SRM University, Chennai, 603203, India. koustav.g@res.srmuniv.ac.in.
authors.forename: Koustav
authors.initials: K
authors.lastname: Ganguly
authors.affiliation: Institute of Lung Biology and Disease, Comprehensive Pneumology Center Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany. schulz@helmholtz-muenchen.de.|Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764, Neuherberg/München, Germany. schulz@helmholtz-muenchen.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
mesh_terms: D000375:Aging; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D002244:Carbon / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis / Q000097:blood / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006973:Hypertension / Q000150:complications*; D018836:Inflammation Mediators / Q000032:analysis / Q000097:blood / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011918:Rats, Inbred SHR; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D065589:Respiratory Tract Absorption; D013047:Specific Pathogen-Free Organisms; D013927:Thrombosis / Q000209:etiology
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D018836:Inflammation Mediators; D052638:Particulate Matter; D002244:Carbon