title: Chronic Exposure to Bisphenol A Reduces Successful Cardiac Remodeling After an Experimental Myocardial Infarction in Male C57bl/6n Mice.
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.
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
authors: Bhavini B
authors: BB
authors: Patel
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
authors: Amanda
authors: A
authors: Kasneci
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
authors: Alicia M
authors: AM
authors: Bolt
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
authors: Vanessa
authors: V
authors: Di Lalla
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
authors: Massimo R
authors: MR
authors: Di Iorio
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
authors: Mohamad
authors: M
authors: Raad
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada.
authors: Koren K
authors: KK
authors: Mann
authors: *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada *Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada, Department of Oncology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada, Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec H3A 1A2, Canada, Division of Cardiology and Division of Endocrinology, Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec H3T 1E2, Canada lorraine.chalifour@mcgill.ca.
authors: Lorraine E
authors: LE
authors: Chalifour
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology*; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: bisphenol A; echocardiography; inflammation; myocardial infarction