d4c474848bc6e46b10525354d6ca21e2 antioxidants-11-00075.pdf ae41872bc508d5c24a867c82a6d570d6d2f421e1 antioxidants-11-00075.pdf 3fd41f96cf51620b6e18a03039ef44a421b05f62110ae3d9575c0a65cfc8c51b antioxidants-11-00075.pdf Title: Human Lysyl Oxidase Over-Expression Enhances Baseline Cardiac Oxidative Stress but Does Not Aggravate ROS Generation or Infarct Size Following Myocardial Ischemia-Reperfusion Subject: Lysyl oxidase (LOX) is an enzyme critically involved in collagen maturation, whose activity releases H2O2 as a by-product. Previous studies demonstrated that LOX over-expression enhances reactive oxygen species (ROS) production and exacerbates cardiac remodeling induced by pressure overload. However, whether LOX influences acute myocardial infarction and post-infarct left ventricular remodeling and the contribution of LOX to myocardial oxidative stress following ischemia-reperfusion have not been analyzed. Isolated hearts from transgenic mice over-expressing human LOX in the heart (TgLOX) and wild-type (WT) littermates were subjected to global ischemia and reperfusion. Although under basal conditions LOX transgenesis is associated with higher cardiac superoxide levels than WT mice, no differences in ROS production were detected in ischemic hearts and a comparable acute ischemia-reperfusion injury was observed (infarct size: 56.24 9.44 vs. 48.63 2.99% of cardiac weight in WT and TgLOX, respectively). Further, similar changes in cardiac dimensions and function were observed in TgLOX and WT mice 28 days after myocardial infarction induced by transient left anterior descending (LAD) coronary artery occlusion, and no differences in scar area were detected (20.29 3.10 vs. 21.83 2.83% of left ventricle). Our data evidence that, although LOX transgenesis induces baseline myocardial oxidative stress, neither ROS production, infarct size, nor post-infarction cardiac remodeling were exacerbated following myocardial ischemia-reperfusion. Keywords: lysyl oxidase; reperfusion injury; cardiac remodeling Author: Laura Valls-Lacalle, Lídia Puertas-Umbert, Saray Varona, José Martínez-González, Cristina Rodríguez and Antonio Rodríguez-Sinovas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Dec 29 08:56:08 2021 CET ModDate: Wed Dec 29 09:02:53 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2806349 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IBTYZX+VnURWPalladioL Type 1 Custom yes yes no 10 0 VROEYO+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 HHGDIY+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 IMJVHC+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 YFFKLH+CMSY10 Type 1 Builtin yes yes no 28 0 IOJCNK+VnURWPalladioL-Bold 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Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 435 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Animals Destination: subsection.2.1 Item: Title: Ischemia-Reperfusion Injury in Isolated Mouse Hearts Destination: subsection.2.2 Children: Item: Title: Experimental Protocol Destination: subsubsection.2.2.1 Item: Title: LDH Release and Infarct Size Measurement Destination: subsubsection.2.2.2 Item: Title: In Situ Mouse Model of Post-Infarct Cardiac Remodeling Destination: subsection.2.3 Children: Item: Title: Transthoracic Echocardiography Destination: subsubsection.2.3.1 Item: Title: Measurement of Scar Area and Cardiomyocyte Cross-Sectional Area Destination: subsubsection.2.3.2 Item: Title: Real-Time PCR Destination: subsection.2.4 Item: Title: Western Blotting Destination: subsection.2.5 Item: Title: Immunohistochemistry Destination: subsection.2.6 Item: Title: ROS Detection Destination: subsection.2.7 Item: Title: Statistics Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: LOX Transgenesis Is Associated with Enhanced Cardiac LOX Protein Levels and ROS Production Destination: subsection.3.1 Item: Title: Impact of Acute Ischemia-Reperfusion Injury on Left Ventricular Function, Infarct Size, and ROS Production in Isolated Mouse Hearts Destination: subsection.3.2 Item: Title: Effect of Human LOX Over-Expression on Mice Survival and Left Ventricular Remodeling in Response to Myocardial Infarction Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Human Lysyl Oxidase Over-Expression Enhances Baseline Cardiac Oxidative Stress but Does Not Aggravate ROS Generation or Infarct Size Following Myocardial Ischemia-Reperfusion Author: Laura Valls-Lacalle, Lídia Puertas-Umbert, Saray Varona, José Martínez-González, Cristina Rodríguez and Antonio Rodríguez-Sinovas Subject: Lysyl oxidase (LOX) is an enzyme critically involved in collagen maturation, whose activity releases H2O2 as a by-product. Previous studies demonstrated that LOX over-expression enhances reactive oxygen species (ROS) production and exacerbates cardiac remodeling induced by pressure overload. However, whether LOX influences acute myocardial infarction and post-infarct left ventricular remodeling and the contribution of LOX to myocardial oxidative stress following ischemia-reperfusion have not been analyzed. Isolated hearts from transgenic mice over-expressing human LOX in the heart (TgLOX) and wild-type (WT) littermates were subjected to global ischemia and reperfusion. Although under basal conditions LOX transgenesis is associated with higher cardiac superoxide levels than WT mice, no differences in ROS production were detected in ischemic hearts and a comparable acute ischemia-reperfusion injury was observed (infarct size: 56.24 9.44 vs. 48.63 2.99% of cardiac weight in WT and TgLOX, respectively). Further, similar changes in cardiac dimensions and function were observed in TgLOX and WT mice 28 days after myocardial infarction induced by transient left anterior descending (LAD) coronary artery occlusion, and no differences in scar area were detected (20.29 3.10 vs. 21.83 2.83% of left ventricle). Our data evidence that, although LOX transgenesis induces baseline myocardial oxidative stress, neither ROS production, infarct size, nor post-infarction cardiac remodeling were exacerbated following myocardial ischemia-reperfusion. 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