Compensatory response of cardiac lysyl oxidase to chronic volume overload

Abstract

Volume overload causes extensive remodeling of the ventricle, with structural and functional alterations. These alterations include disruption of extracellular collagen, ventricular hypertrophy and dilatation, and eventual heart failure. The collagen crosslinking enzyme, lysyl oxidase (LOX), is necessary for collagen maturation, but little is known about its role in the remodeling heart. We hypothesized that chronic volume overload induced remodeling and dysfunction are accompanied by elevations of cardiac LOX protein expression and activity. Surgically induced volume overload and sham‐operated rats were studied at 4, 14 and 21 wks post‐surgery. Ultrasound was used to evaluate cardiac function. Left ventricular (LV) LOX expression and activity were determined by Western blot and Amplex red assay, respectively. Collagen content was determined by picrosirius red assay. Volume overload caused progressive ventricular dilatation and dysfunction. LV LOX protein expression was elevated after 4, 14 and 21 wks of volume overload (30%, 65% and 92% increases vs. sham, p<0.05). This elevation correlated with increased LOX activity at 4 and 14 wks, but not at 21 wks. Despite increased LOX expression and activity, a progressive loss of collagen was observed. These data indicate that compensatory increases in LOX occur in response to volume overload, but are insufficient to prevent collagen loss and dilatation.