Abstract 18196: Aldehyde Oxidase is a Potent Source of Superoxide Generation and Can Modulate Cardiac Contractile Function
Aldehyde oxidase (AO) is a cytosolic enzyme belonging to the xanthine oxidoreductase (XOR) family. A variety of aldehyde substrates are known to be formed in cardiovascular disease secondary to inflammation and oxidative stress that are efficient AO substrates. While XOR has been reported to influence heart function in heart failure and is well known to be an important source of superoxide (O2•-), little is known regarding the role of AO in cardiac oxidant signaling. In order to assess the presence of AO in the heart and its potential role in cardiovascular pathophysiology, we studied the distribution of AO in rat myocardium and isolated cardiac myocytes as well as its levels and activities in heart tissue. Furthermore, in isolated perfused rat hearts we measured the functional effect of AO activation or inhibition. Immunohistochemistry, using an AO specific antibody, showed a myofibrillar / sarcomere distribution for AO. In control rat myocardium, the activity of AO was found to be 1.5-fold higher than that of total XOR (0.21±0.02 vs. 0.14±0.01 nmol min-1 mg-1 of protein), and the levels of protein 2.5-fold higher than that of XOR (30.26±2.42 vs. 11.86±1.07 nM), while O2•- production (measured by cytochrome c assay) in the presence of optimal substrate levels was estimated to be >10-fold higher for AO than XOR. In isolated perfused rat hearts, infusion with the AO substrate 4-(dimethylamino)cinnamaldehyde (p-DMAC) (10 μM) resulted in a significant increase in left ventricular developed pressure (LVDP) of 14±3% (p<0.05), while treatment with the potent inhibitor amadone (10 μM) completely inhibited this increase. Thus, AO is present in cardiac myocytes adjacent to the contractile proteins and in the presence of aldehyde substrates it can function as an important source of O2•- modulating contractile function. Further studies will be needed to assess the potential role of AO in modulating cardiac function in ischemic syndromes and heart failure.
- © 2011 by American Heart Association, Inc.