Chronic Exposure to Bisphenol A Reduces Successful Cardiac Remodeling After an Experimental Myocardial Infarction in Male C57bl/6n Mice

Toxicol Sci. 2015 Jul;146(1):101-15. doi: 10.1093/toxsci/kfv073. Epub 2015 Apr 9.

Abstract

Estrogenic compounds such as bisphenol A (BPA) leach from plastics into food and beverage containers. Increased BPA exposure has been correlated with increased cardiovascular disease. To test the hypothesis that increased BPA exposure reduces cardiovascular remodeling, we chronically exposed C57bl/6n male mice to BPA and performed a myocardial infarction (MI). We measured cardiac function, as well as myeloid and cardiac fibroblast accumulation and activity. We found increased early death as well as increased cardiac dilation and reduced cardiac function in surviving BPA-exposed mice. Matrix metalloproteinase-2 (MMP2) protein and activity were increased 1.5-fold in BPA-exposed heart. BPA-exposed mice had similar neutrophil infiltration; however, monocyte and macrophage (MΦ) infiltration into the ischemic area was 5-fold greater than VEH mice potentially due to a 2-fold increase in monocyte chemoattractant protein-1. Monocyte and MΦ exposure to BPA in vitro in primary bone marrow cultures or in isolated peritoneal MΦ increased polarization to an activated MΦ, increased MMP2 and MMP9 expression 2-fold and activity 3-fold, and increased uptake of microspheres 3-fold. Cardiac fibroblasts (CF) differentiate to α-smooth muscle actin (αSMA) expressing myofibroblasts, migrate to the ischemic area and secrete collagen to strengthen the scar. Collagen and αSMA expression were reduced 50% in BPA-exposed hearts. Chronic in vivo or continuous in vitro BPA exposure ablated transforming growth factor beta-mediated differentiation of CF, reduced αSMA expression 50% and reduced migration 40% yet increased secreted MMP2 activity 2-fold. We conclude that chronic BPA exposure reduces the ability to successfully remodel after an MI by increasing MΦ-based inflammation and reducing myofibroblast repair function.

Keywords: bisphenol A; echocardiography; inflammation; myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / toxicity*
  • Heart / drug effects*
  • Heart Function Tests
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / physiopathology*
  • Phenols / administration & dosage
  • Phenols / toxicity*

Substances

  • Benzhydryl Compounds
  • Phenols
  • bisphenol A