In Utero Particulate Matter Exposure Produces Heart Failure, Electrical Remodeling, and Epigenetic Changes at Adulthood

Autor: Markus Velten, Cynthia A. Carnes, Mark T. Ziolo, Stephen Baine, Clayton M. Eichenseer, Matthew W. Gorr, Victor P. Long, Loren E. Wold, Ingrid M. Bonilla, Vikram Shettigar, Vineeta Tanwar, Jonathan P. Davis
Rok vydání: 2017
Předmět:
0301 basic medicine
air pollution
Action Potentials
heart failure
030204 cardiovascular system & hematology
Calcium Cycling/Excitation-Contraction Coupling
Ventricular Function
Left
Molecular Cardiology
DNA Methyltransferase 3A
Epigenesis
Genetic
Mice
Sirtuin 2
0302 clinical medicine
Sirtuin 1
Heart Rate
Pregnancy
Myocytes
Cardiac
DNA (Cytosine-5-)-Methyltransferases
Phosphorylation
Original Research
myocyte
Inhalation Exposure
Ventricular Remodeling
Age Factors
myocardial
Particulates
Maternal Exposure
In utero
Prenatal Exposure Delayed Effects
Cardiology
Female
Cardiology and Cardiovascular Medicine
Cardiovascular outcomes
DNA (Cytosine-5-)-Methyltransferase 1
medicine.medical_specialty
cardiac
Gestational Age
Calcium-Transporting ATPases
calcium signaling
in utero
Sodium-Calcium Exchanger
03 medical and health sciences
Internal medicine
medicine
Animals
Electrical Remodeling
Epigenetics
Particle Size
cardiovascular function
particulate matter
business.industry
Calcium-Binding Proteins
Arrhythmias
Cardiac
Atrial Remodeling
medicine.disease
030104 developmental biology
Endocrinology
Animals
Newborn
Animal Models of Human Disease
Heart failure
Contractile function
business
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
DOI: 10.1161/jaha.117.005796
Popis: Background Particulate matter (PM; PM 2.5 [PM with diameters of PM 2.5 exposure alone could alter cardiac structure and function at adulthood. Methods and Results Female FVB mice were exposed either to filtered air or PM 2.5 at an average concentration of 73.61 μg/m 3 for 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 /dt max /end‐systolic volume), frequency‐dependent acceleration of relaxation), and blunted contractile response to β‐adrenergic stimulation in PM 2.5 ‐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 PM 2.5 ‐exposed mice at adulthood. Cardiac interleukin ( IL) ‐6, IL ‐1ß, collagen‐1, matrix metalloproteinase ( MMP ) 9, and MMP 13 gene expressions were increased at birth in in utero PM 2.5 ‐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 Ca 2+ ‐ATPase, phosphorylated phospholamban, and Na + /Ca 2+ exchanger were decreased. Conclusions In utero PM 2.5 exposure triggers an acute inflammatory response, chronic matrix remodeling, and alterations in Ca 2+ handling proteins, resulting in global adult cardiac dysfunction. These results also highlight the potential involvement of epigenetics in priming of adult cardiac disease.
Databáze: OpenAIRE
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