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.