RATIONALE: Telomerase is a nuclear regulator of telomere elongation with recent reports suggesting a role in regulation of mitochondrial reactive @entity26 species (mtROS). Since mtROS ( @entity5568 ) mediate @entity384 ( @entity384 ) in the @entity1 microcirculation. OBJECTIVE: We examined the hypothesis that telomerase activity modulates microvascular @entity384 and loss of telomerase activity contributes to the change of mediator from @entity842 (NO) to mt @entity5568 in @entity1 with @entity453 ( @entity453 ). METHODS AND RESULTS: @entity1 coronary and adipose arterioles were isolated for videomicroscopy. @entity384 was measured in vessels pre-treated with the telomerase inhibitor @entity25083 or vehicle. Statistical differences between groups were determined using a two-way ANOVA (n>= 4; P<0.05). @entity6462 (NO synthase inhibitor) abolished @entity384 in arterioles from subjects without @entity453 , while @entity970 -Catalase ( @entity5568 scavenger) had no effect. Following exposure to @entity25083 , arterioles from non- @entity453 subjects maintained the magnitude of dilation but changed the mediator from NO to mt @entity5568 (% max diameter at 100 cm @entity4358 : Vehicle 74.6  4.1, @entity6462 37.0  2.0*, @entity970 -Catalase 82.1  2.8; @entity25083 69.9  4.0, @entity6462 84.7  2.2, @entity970 -Catalase 36.5  6.9*). Conversely, treatment of microvessels from @entity453 @entity1 with the telomerase activator @entity69301 converted the @entity970 -catalase-inhibitable dilation to one mediated by NO (% max diameter at 100 cm @entity4358 : Adipose, @entity69301 78.5  3.9; @entity6462 10.9  17.5*; @entity970 -Catalase 79.2  4.9). Endothelial-independent dilation was not altered with either treatment. CONCLUSIONS: We have identified a novel role for telomerase in re-establishing a physiological mechanism of vasodilation in arterioles from subjects with @entity453 . These findings suggest a new target for reducing the oxidative milieu in the microvasculature of @entity1 with @entity453 .

Critical Role for Telomerase in the Mechanism of Flow Mediated Dilation in the XXXX Microcirculation.

@entity1 :: ('9606', 'Species') :: ['human', 'patients', 'Human'] @entity5568 :: ('D006861', 'Chemical') :: ['H2O2'] @entity69301 :: ('MESH:C573922', 'Chemical') :: ['AGS-499', 'AGS 499'] @entity4358 :: ('D014867', 'Chemical') :: ['H2O'] @entity384 :: ('MESH:D002311', 'Disease') :: ['flow-mediated dilation', 'FMD'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity25083 :: ('MESH:C458523', 'Chemical') :: ['BIBR-1532'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity453 :: ('MESH:D003324', 'Disease') :: ['CAD', 'coronary artery disease'] @entity6462 :: ('D019331', 'Chemical') :: ['L-NAME'] @entity970 :: ('CHEBI:46793', 'Chemical') :: ['Peg', 'PEG']
@entity1 :: (9606,Species) :: ['Human']
