Human Lysyl Oxidase Over-Expression Enhances Baseline Cardiac Oxidative Stress but Does Not Aggravate ROS Generation or Infarct Size Following Myocardial Ischemia-Reperfusion
Open Access
- 29 December 2021
- journal article
- research article
- Published by MDPI AG in Antioxidants
- Vol. 11 (1) , 75
Abstract
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
Funding Information
- Instituto de Salud Carlos III (PI18/0919, PI17/01397)
- Spanish Ministerio de Ciencia e Innovación (RTI2018-094727-B-100)
- Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR-00333, 2017-SGR-1807)
- Fundació la Marató TV3 (2015.3610)
This publication has 36 references indexed in Scilit:
- Endothelial NADPH Oxidase-2 Promotes Interstitial Cardiac Fibrosis and Diastolic Dysfunction Through Proinflammatory Effects and Endothelial-Mesenchymal TransitionJACC, 2014
- Left and Right Ventricle Late Remodeling Following Myocardial Infarction in RatsPLOS ONE, 2013
- Activation of RISK and SAFE pathways is not involved in the effects of Cx43 deficiency on tolerance to ischemia–reperfusion injury and preconditioning protectionBasic Research in Cardiology, 2013
- Myocardial ischemia-reperfusion injury: a neglected therapeutic targetJournal of Clinical Investigation, 2013
- Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart FailureHypertension, 2012
- The Extracellular Matrix: Not Just Pretty FibrilsScience, 2009
- Mechanical Unloading During Left Ventricular Assist Device Support Increases Left Ventricular Collagen Cross-Linking and Myocardial StiffnessCirculation, 2005
- The role of myocardial fibrillar collagen in ventricular remodeling and functionJournal of Cardiac Failure, 2002
- Collagen network remodelling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophyCardiovascular Research, 1988
- Connective tissue content and myocardial stiffness in pressure overload hypertrophy A combined study of morphologic, morphometric, biochemical, and mechanical parametersBasic Research in Cardiology, 1983