title: In Utero Particulate Matter Exposure Produces Heart Failure, Electrical Remodeling, and Epigenetic Changes at Adulthood.
abstract: BACKGROUND
  Particulate matter (PM; PM2.5[PM with diameters of <2.5 μm]) exposure during development is strongly associated with adverse cardiovascular outcomes at adulthood. In the present study, we tested the hypothesis that in utero PM2.5exposure alone could alter cardiac structure and function at adulthood.
  
  
  RESULTS
  Female FVB mice were exposed either to filtered air or PM2.5at an average concentration of 73.61 μg/m3for 6 h/day, 7 days/week throughout pregnancy. After birth, animals were analyzed at 12 weeks of age. Echocardiographic (n=9-10 mice/group) and pressure-volume loop analyses (n=5 mice/group) revealed reduced fractional shortening, increased left ventricular end-systolic and -diastolic diameters, reduced left ventricular posterior wall thickness, end-systolic elastance, contractile reserve (dP/dtmax/end-systolic volume), frequency-dependent acceleration of relaxation), and blunted contractile response to β-adrenergic stimulation in PM2.5-exposed mice. Isolated cardiomyocyte (n=4-5 mice/group) function illustrated reduced peak shortening, ±dL/dT, and prolonged action potential duration at 90% repolarization. Histological left ventricular analyses (n=3 mice/group) showed increased collagen deposition in in utero PM2.5-exposed mice at adulthood. Cardiac interleukin (IL)-6, IL-1ß, collagen-1, matrix metalloproteinase (MMP) 9, and MMP13 gene expressions were increased at birth in in utero PM2.5-exposed mice (n=4 mice/group). In adult hearts (n=5 mice/group), gene expressions of sirtuin (Sirt) 1 and Sirt2 were decreased, DNA methyltransferase (Dnmt) 1, Dnmt3a, and Dnmt3b were increased, and protein expression (n=6 mice/group) of Ca2+-ATPase, phosphorylated phospholamban, and Na+/Ca2+exchanger were decreased.
  
  
  CONCLUSIONS
  In utero PM2.5exposure triggers an acute inflammatory response, chronic matrix remodeling, and alterations in Ca2+handling proteins, resulting in global adult cardiac dysfunction. These results also highlight the potential involvement of epigenetics in priming of adult cardiac disease.
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH.|College of Nursing, The Ohio State University, Columbus, OH.
authors.forename: Vineeta
authors.initials: V
authors.lastname: Tanwar
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH.|College of Nursing, The Ohio State University, Columbus, OH.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Gorr
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Rheinische Friedrich-Wilhelms-University, University Medical Center, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH.|College of Nursing, The Ohio State University, Columbus, OH.
authors.forename: Clayton M
authors.initials: CM
authors.lastname: Eichenseer
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH.|College of Pharmacy, The Ohio State University, Columbus, OH.
authors.forename: Victor P
authors.initials: VP
authors.lastname: Long
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Bonilla
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH.
authors.forename: Vikram
authors.initials: V
authors.lastname: Shettigar
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ziolo
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Davis
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, OH.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Baine
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH.|College of Pharmacy, The Ohio State University, Columbus, OH.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, OH loren.wold@osumc.edu.|Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH.|College of Nursing, The Ohio State University, Columbus, OH.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D064752:Atrial Remodeling / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D006333:Heart Failure / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects*; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects; D000097584:DNA Methyltransferase 3B; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D052638:Particulate Matter; D056564:Sirtuin 1; D056565:Sirtuin 2; D019831:Sodium-Calcium Exchanger; D000097584:DNA Methyltransferase 3B; D000099211:Phospholamban; C000715535:Dnmt3a protein, mouse; C470545:Sirt1 protein, mouse; C418743:Sirt2 protein, mouse
keywords: air pollution; calcium signaling; cardiac; cardiovascular function; heart failure; in utero; myocardial; myocyte; particulate matter