No abstract

LAA closure with the LARIAT device can be performed effectively with acceptably low access complications and periprocedural adverse events in this observational study.

Objectives To examine the expression and activity of the calcium dependent NADPH oxidase in human atherosclerotic coronary arteries. Background The Nox based NADPH oxidases are major sources of reactive oxygen species (ROS) in human vessels. Several Nox homologs have been identified but their relative contribution to vascular ROS production in coronary artery disease (CAD) is unclear. Nox5 is a unique homolog in that it is calcium dependent and thus could be activated by vasoconstrictor hormones. Its presence has not yet been studied in human vessels. Methods Coronary arteries from patients undergoing cardiac transplant with CAD or without CAD were studied. Nox5 was quantified and visualized using Western blotting, immunofluorescence and quantitative real-time PCR. Calcium dependent NADPH oxidase activity, corresponding greatly to Nox5 activity was measured by electron paramagnetic resonance. Results Both western blotting and quantitative real time PCR indicated a marked increase in Nox5 protein and mRNA in CAD vs non CAD vessels. Calcium dependent NADPH driven production of reactive oxygen species in vascular membranes, reflecting Nox5 activity was increased 7 fold in CAD and correlated significantly with Nox5 mRNA levels among subjects. Immunofluorescence demonstrated that Nox5 was expressed in the endothelium in the early lesions and in vascular smooth muscle cells in the advanced in coronary lesions. Conclusions These studies identify Nox5 as a novel, calcium dependent source of reactive oxygen species in atherosclerosis.

Background-Oxidative stress plays important role in the pathogenesis of atherosclerosis and coronary artery disease (CAD). We aimed to determine the sources and selected molecular mechanisms of oxidative stress in CAD. Methods and Results-We examined basal and NAD(P)H oxidase-mediated superoxide (O 2 · Ϫ ) production using lucigenin chemiluminescence, ferricytochrome c and dihydroethidium fluorescence in human coronary arteries from 19 CAD and 17 non-CAD patients undergoing heart transplantation. NAD(P)H oxidase subunits and xanthine oxidase expression were measured. Superoxide production was greater in coronary arteries from patients with CAD, even in vessels without overt atherosclerotic plaques, and was doubled within branching points of coronary arteries. Studies using pharmacological inhibitors and specific substrates showed that NAD(P)H oxidases (60%) and xanthine oxidase (25%) are primary sources of O 2 · Ϫ in CAD. Losartan significantly inhibited superoxide production in coronary arteries. NAD(P)H oxidase activity and protein levels of the NADPH oxidase subunits p22phox, p67phox, and p47phox were significantly increased in CAD, as were mRNA levels for p22phox and nox2, and no NAD(P)H oxidase subunit mRNA levels correlated with NAD(P)H oxidase activity in vessels from individual patients. Activity and protein expression of xanthine oxidase were increased in CAD, whereas xanthine dehydrogenase levels were not changed. Key Words: endothelium Ⅲ NAD(P)H oxidase Ⅲ nitric oxide Ⅲ oxidant stress Ⅲ reactive oxygen species I ncreased vascular production of reactive oxygen species is a characteristic feature of vascular disease states, including coronary artery disease (CAD). In particular, superoxide (O 2 · Ϫ ) and products of O 2 · Ϫ promote atherosclerosis by quenching nitric oxide (NO) and activating redox-sensitive signaling pathways 1 that modulate vessel remodeling and plaque stability. 2 Accordingly, endothelial dysfunction associated with overproduction of O 2 · Ϫ has been shown to provide prognostic information in patients with coronary artery disease. 3,4 Potential sources of vascular O 2 · Ϫ include the NAD(P)H oxidases, xanthine oxidase, cyclooxygenases, nitric oxide synthases, or mitochondrial oxidases. 5 Recent studies have shown that the NAD(P)H oxidases and xanthine oxidase have important roles in human vessels. 6 Azumi et al first showed that NAD(P)H oxidase is present in human coronary arteries. 7 Several molecular homologues of the NAD(P)H oxidase large membrane subunit, (gp91phox; nox2) are present in vascular cells, 5 and could contribute to ROS production during development of CAD. More recent studies have shown that NAD(P)H oxidase subunit expression is correlated with both severity of atherosclerosis 5 and with features of plaque stability in human coronary arteries. 8 Despite these important findings, a systematic analysis of the sources of O 2 · Ϫ production in human coronary arteries is lacking. Furthermore, it is not clear how coronary O 2 · Ϫ production is regulated in the presence of ...