The lysyl oxidase inhibitor (β-aminopropionitrile) reduces leptin profibrotic effects and ameliorates cardiovascular remodeling in diet-induced obesity in rats - PubMed (original) (raw)
The lysyl oxidase inhibitor (β-aminopropionitrile) reduces leptin profibrotic effects and ameliorates cardiovascular remodeling in diet-induced obesity in rats
Ernesto Martínez-Martínez et al. J Mol Cell Cardiol. 2016 Mar.
Abstract
Lysyl oxidase (LOX) is an extracellular matrix (ECM)-modifying enzyme that has been involved in cardiovascular remodeling. We explore the impact of LOX inhibition in ECM alterations induced by obesity in the cardiovascular system. LOX is overexpressed in the heart and aorta from rats fed a high-fat diet (HFD). β-Aminopropionitrile (BAPN), an inhibitor of LOX activity, significantly attenuated the increase in body weight and cardiac hypertrophy observed in HFD rats. No significant differences were found in cardiac function or blood pressure among any group. However, HFD rats showed cardiac and vascular fibrosis and enhanced levels of superoxide anion (O2(-)), collagen I and transforming growth factor β (TGF-β) in heart and aorta and connective tissue growth factor (CTGF) in aorta, effects that were attenuated by LOX inhibition. Interestingly, BAPN also prevented the increase in circulating leptin levels detected in HFD fed animals. Leptin increased protein levels of collagen I, TGF-β and CTGF, Akt phosphorylation and O2(-) production in both cardiac myofibroblasts and vascular smooth muscle cells in culture, while LOX inhibition ameliorated these alterations. LOX knockdown also attenuated leptin-induced collagen I production in cardiovascular cells. Our findings indicate that LOX inhibition attenuates the fibrosis and the oxidative stress induced by a HFD on the cardiovascular system. The reduction of leptin levels by BAPN in vivo and the ability of this compound to inhibit leptin-induced profibrotic mediators and ROS production in cardiac and vascular cells suggest that interactions between leptin and LOX regulate downstream events responsible for myocardial and vascular fibrosis in obesity.
Keywords: Fibrosis; Leptin; Lysyl oxidase; Obesity.
Copyright © 2016 Elsevier Ltd. All rights reserved.
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