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

Abstract

BackgroundParticulate matter (PM; PM 2.5 [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 PM 2.5 exposure alone could alter cardiac structure and function at adulthood.Methods and ResultsFemale FVB mice were exposed either to filtered air or PM 2.5 at an average concentration of 73.61 μg/m3 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/dtmax/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 MMP13 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 Ca2+‐ATPase, phosphorylated phospholamban, and Na+/Ca2+ exchanger were decreased.ConclusionsIn utero PM 2.5 exposure 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.