Telomerase is a nuclear regulator of telomere elongation with recent reports suggesting a role in regulation of mitochondrial reactive oxygen species (mtROS). Since mtROS (H2O2) mediate flow-mediated dilation (FMD) in the human microcirculation.
We examined the hypothesis that telomerase activity modulates microvascular FMD and loss of telomerase activity contributes to the change of mediator from nitric oxide (NO) to mtH2O2 in patients with coronary artery disease (CAD).
Human coronary and adipose arterioles were isolated for videomicroscopy. FMD was measured in vessels pre-treated with the telomerase inhibitor BIBR-1532 or vehicle. Statistical differences between groups were determined using a two-way ANOVA (n≥4; P<0.05). L-NAME (NO synthase inhibitor) abolished FMD in arterioles from subjects without CAD, while PEG-Catalase (H2O2 scavenger) had no effect. Following exposure to BIBR-1532, arterioles from non-CAD subjects maintained the magnitude of dilation but changed the mediator from NO to mtH2O2 (% max diameter at 100 cm H2O: 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 NO (% max diameter at 100 cm H2O: 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.
We have identified a novel role for telomerase in re-establishing a physiological mechanism of vasodilation in arterioles from subjects with CAD. These findings suggest a new target for reducing the oxidative milieu in the microvasculature of patients with CAD.
Pharmacology, Toxicology and Pharmaceutical Science
5
7%
Nursing and Health Professions
3
4%
Other
7
10%
Unknown
20
29%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 March 2016.
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#19,944,994
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#6,896
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#275,919
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Outputs of similar age from Circulation Research
#60
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