کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5533657 | 1550397 | 2017 | 10 صفحه PDF | دانلود رایگان |
- Cardiac lysyl oxidase (LOX) expression and activity progressively increased in response to chronic volume overload (VO)
- Chronic VO elevated cardiac LOX expression and activity which increased myocardial collagen and collagen cross-linking.
- Inhibition of LOX activity completely prevented VO-induced fibrosis and cardiac dysfunction.
- Excessive LOX activity may contribute to the decline in cardiac function leading to heart failure.
A key feature of heart failure is adverse extracellular matrix (ECM) remodeling, which is associated with increases in the collagen cross-linking enzyme, lysyl oxidase (LOX). In this study, we assess the progression of cardiovascular remodeling from the compensatory to decompensatory phase, with a focus on the change in LOX expression and activity as it relates to alterations in ECM composition and changes in cardiac function. Adult male Sprague-Dawley rats were studied after 4, 14, or 21Â weeks of aortocaval fistula-induced volume overload (VO). Progressive increases in the left and right ventricular mass indicated biventricular hypertrophy. Echocardiography revealed significant increases in the posterior wall thickness and internal diameter of the left ventricle as early as 3Â weeks, which persisted until the 21Â week endpoint. There were also significant decreases in eccentric index and fractional shortening in VO animals. Hemodynamic measurements showed progressive decreases in contractility, indicative of systolic dysfunction. There were progressive VO-induced increases in LOX expression and activity, collagen, and collagen cross-linking during the course of these experiments. We observed a negative correlation between LOX activity and cardiac function. Additional rats were treated with an inhibitor of LOX activity starting at 2Â weeks post-surgery and continued to 14Â weeks. LOX inhibition prevented the cardiac dysfunction and collagen accumulation caused by VO. Overall these data suggest a detrimental role for the chronic increase of cardiac LOX expression and activity in the transition from compensated remodeling to decompensated failure.
Journal: Journal of Molecular and Cellular Cardiology - Volume 109, August 2017, Pages 17-26