Not all of the effects of telomerase can be easily explained by its nuclear actions. Growing evidence suggests that TERT, the catalytic subunit of telomerase, can reversibly translocate from the nucleus to organelles (including the mitochondria), in a dose-and time-dependent manner, in response to stressors, Objective: We examined the hypothesis that telomerase activity modulates microvascular flow-mediated dilation, and loss of telomerase activity contributes to the change of mediator from nitric oxide to mitochondrial hydrogen peroxide in patients with coronary artery disease (CAD). Clinical Track Methods and Results:Human coronary and adipose arterioles were isolated for videomicroscopy. Flow-mediated dilation was measured in vessels pretreated with the telomerase inhibitor BIBR-1532 or vehicle. Statistical differences between groups were determined using a 2-way analysis of variance repeated measure (n≥4; P<0.05). L-NAME (N ω -nitro-L-arginine methyl ester; nitric oxide synthase inhibitor) abolished flow-mediated dilation in arterioles from subjects without CAD, whereas polyethylene glycol-catalase (PEG-catalase; hydrogen peroxide scavenger) had no effect. After exposure to BIBR-1532, arterioles from non-CAD subjects maintained the magnitude of dilation but changed the mediator from nitric oxide to mitochondrial hydrogen peroxide (% max diameter at 100 cm H 2 O: vehicle 74.6±4.1, L-NAME 37.0±2.0*, PEG-catalase 82.1±2.8; BIBR-1532 69.9±4.0, L-NAME 84.7±2.2, PEG-catalase 36.5±6.9*). Conversely, treatment of microvessels from CAD patients with the telomerase activator AGS 499 converted the PEG-catalase-inhibitable dilation to one mediated by nitric oxide (% max diameter at 100 cm H 2 O: adipose, AGS 499 78.5±3.9; L-NAME 10.9±17.5*; PEG-catalase 79.2±4.9). Endothelial-independent dilation was not altered with either treatment. Conclusions:

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Despite equality between sexes in early outcome and superiority of female sex in long-term survival, there were 3 independent predictors for long-term mortality after coronary artery bypass grafting unique for women compared with 12 for men. Clinical decision making and follow-up should not be influenced by stereotypes but by specific findings.

Cardiopulmonary bypass with hypothermic circulatory arrest can safely be used in the treatment of complex adult coarctation. It permits accurate delineation of the anatomy with minimal dissection, avoidance of aortic clamping and sacrifice of intercostal arteries, precise interposition graft repair, and adequate protection of vital organs.

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