Premium
Preconception Exposure of Particulate Matter Leads to Adult Cardiac Dysfunction through Altering Myocyte Function and Ca2 + Signaling Pathways
Author(s) -
tanwar vineeta,
Adelstein Jeremy,
Sugar Benjamin,
Schwieterman Neill,
Youtz Dane,
Falvo Michael,
Wold Loren
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.901.3
Subject(s) - cardiac function curve , offspring , in utero , particulates , medicine , in vivo , endocrinology , myocyte , cardiac myocyte , andrology , chemistry , zoology , cardiology , pregnancy , biology , heart failure , fetus , genetics , organic chemistry
Objective Previous studies have demonstrated that particulate matter, or ambient particles less than 2.5 μm (PM 2.5 ) in diameter, exposure during both in utero and postnatal developmental periods triggers electrical remodeling and cardiac dysfunction during adulthood. This shows that PM 2.5 can reprogram hearts during the gestational period. Despite this evidence, cardiac effects from pre‐gestational particulate matter exposure remain inconclusive. This study was performed to further investigate the potential priming effects of preconception exposure of PM 2.5 on global cardiac dysfunction at adulthood. METHODS Male and female FVB mice were exposed separately to either filtered air (FA) or PM 2.5 at a concentration (within the annual average range of 15 μg/m 3 according to the National Ambient Air Quality Standards (NAAQS)) for 3 months. Mice were then cross bred into two groups: (1) FAm X FAf (both parents were FA exposed) and, (2) PMm X PMf (both parents were PM exposed). Offspring born to these crosses (PC FA and PC PM 2.5 ) were analyzed at 3 months of age for in vivo cardiac function via echocardiography, followed by in vitro cardiomyocyte functional and molecular analyses. RESULTS Echocardiography identified increased LVESd (2.58 ± 0.13 PC FA, 2.93 ± 0.13 PC PM 2.5 , P=0.1) and reduced PWTs (1.70 ± 0.06 PC FA, 1.44 ± 0.08 PC PM 2.5 , P=0.05) dimensions in PC PM 2.5 ‐exposed mice. Morphological alterations were associated with lower systolic function indicated by reduced fractional shortening % (35.09% ± 1.34 PC FA, 29.05% ± 1.25 PC PM 2.5 , P=0.03) and ejection fraction % (64.86% ± 1.76 PC FA, 56.27% ± 1.95 PC PM 2.5 , P=0.03) in PM 2.5‐ exposed mice. Cardiomyocytes isolated from PC PM 2.5 mice showed reduced peak shortening %PS (12.93% ± 0.42 PC FA, 11.10% ± 0.41 PC PM 2.5 , P=0.002), −dL/dT (−10.60 ± 0.82 PC FA, −8.50 ± 0.60 PC PM 2.5 , P=0.05), TPS90 (0.08 ± 0.003 PC FA, 0.07 ± 0.002 PC PM 2.5 , P=0.05) and slower calcium reuptake (tau, 0.42±0.06 s FA, 0.67±0.09 s PC PM 2.5 , P=0.05). qPCR analyses revealed decreased MURC, MyBPC3 and increased Mypt1 expression and western blot analyses demonstrated modified NCX, SERCA and PLN expression in PC PM 2.5 ‐exposed mice compared to PC FA‐exposed mice. CONCLUSION Similar to our previous study involving in utero exposure, preconception exposure to PC PM 2.5 at real‐world concentrations results in adult cardiac dysfunction. These results suggest that abnormalities in developmental potential are not limited to prenatal or postnatal period but can also be determined prior to conception. Support or Funding Information This work is supported by funding from National Institutes of Health (RO1ES019923) to LEW. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .