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Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer\u2010term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also occur in the heart. At 3\u00a0months of age, nicotine\u2010exposed offspring had 45% decreased PDI levels in the absence of endoplasmic reticulum stress. Given the association of PDI and superoxide dismutase enzymes, we further observed that antioxidant superoxide dismutase\u20102 levels were reduced by 32% in these offspring concomitant with a 26\u201349% decrease in mitochondrial complex proteins (I, II, IV and V) and tissue inhibitor of metalloproteinase\u20104, a critical matrix metalloprotease for cardiac contractility and health. Collectively, this study suggests that perinatal nicotine exposure decreases PDI, which can promote oxidative damage and mitochondrial damage, associated with a premature decline in cardiac function.<\/jats:p>","DOI":"10.1002\/jat.3503","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T05:28:42Z","timestamp":1499318922000},"page":"1517-1526","source":"Crossref","is-referenced-by-count":21,"title":["Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring"],"prefix":"10.1002","volume":"37","author":[{"given":"Nicole G.","family":"Barra","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Lisyansky","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor A.","family":"Vanduzer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology McMaster University  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"Raha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McMaster University  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-5325","authenticated-orcid":false,"given":"Alison C.","family":"Holloway","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology McMaster University  Hamilton Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-273X","authenticated-orcid":false,"given":"Daniel B.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  London Ontario Canada"},{"name":"Departments of Obstetrics and Gynecology, Children's Health Research Institute, Lawson, Health Research Institute Western University  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.05.003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0728"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603393200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062209-093836"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.02.010"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003371"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12901"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2014.09.013"},{"key":"e_1_2_7_10_1","article-title":"Smoking during pregnancy: Findings from the 2009\u20102010 Canadian community health survey","volume":"9","author":"Cui Y.","year":"2014","journal-title":"PloS One"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2012.05.100"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2014.973846"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01345.2007"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.02.080"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2006.09.006"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/735206"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/63.4.350"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2012.06.021"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.05.044"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2005.77"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.10.002"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:30:2:213"},{"issue":"4","key":"e_1_2_7_23_1","first-page":"E443","article-title":"Characterization of the adverse effects of nicotine on placental development: In vivo and in vitro studies. 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