期刊
REPRODUCTIVE SCIENCES
卷 18, 期 11, 页码 1103-1110出版社
SPRINGER HEIDELBERG
DOI: 10.1177/1933719111404605
关键词
collagen; cardiac remodeling; reactive oxygen species; N-acetylcysteine
资金
- National Heart, Lung and Blood Institute [NIH RO1 HL49999, NIH RO1 HL85037, F31 HL090044]
- University of Maryland Statewide Health Network/Other Tobacco-Related Diseases
This study tested the hypothesis that maternal nicotine ingestion increases matrix metalloproteinase (MMP) expression in fetal hearts, which is mediated by the generation of reactive oxygen species. Timed pregnant guinea pigs were administered either water alone, nicotine (200 mg/mL), N-acetylcysteine (NAC), or nicotine plus NAC in their drinking water for 10 days at 52-day gestation (term 65 days). Near-term (62 days), anesthetized fetuses were extracted, hearts were excised, and left cardiac ventricles snap frozen for analysis of MMP-2/-9/-13 protein and activity levels. Interstitial collagens were identified by Picrosirius red stain to assess changes in the extracellular matrix. Prenatal nicotine increased active MMP-2 forms and interstitial collagen but had no effect on either pro-or active MMP-9 or MMP-13 forms. In the presence of nicotine, NAC decreased active MMP-2 protein levels and reversed the nicotine-induced increase in collagen staining. We conclude that prenatal nicotine alters MMP-2 expression in fetal hearts that may be mediated by reactive oxygen species generation.
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