title: Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: Angiotensin-II type-I receptor as a molecular target of particulate matter exposure.
abstract: BACKGROUND
  Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS.
  
  
  METHODS
  Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1).
  
  
  RESULTS
  The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness.
  
  
  CONCLUSIONS
  We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. gammaztatzi@gmail.com.
authors.forename: Octavio Gamaliel
authors.initials: OG
authors.lastname: Aztatzi-Aguilar
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. tmuribe@yahoo.com.
authors.forename: Marisela
authors.initials: M
authors.lastname: Uribe-Ramírez
authors.affiliation: Departamento de Fisiología, Neurociencias y Biofísica, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, C.P. 07360, Mexico. jaarias@fisio.cinvestav.mx.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Arias-Montaño
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. obarbier@cinvestav.mx.
authors.forename: Olivier
authors.initials: O
authors.lastname: Barbier
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. avizcaya@cinvestav.mx.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Vizcaya-Ruiz
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D019570:Inhalation Exposure / Q000009:adverse effects; D016234:Kallikrein-Kinin System / Q000187:drug effects* / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
chemical_list: D000199:Actins; D000975:Antioxidants; C577828:COL3A1 protein, rat; D024061:Collagen Type III; D016207:Cytokines; D052638:Particulate Matter; D012333:RNA, Messenger