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Transition in the mechanism of flow-mediated dilation with aging and development of coronary artery disease.

Authors :
Beyer AM
Zinkevich N
Miller B
Liu Y
Wittenburg AL
Mitchell M
Galdieri R
Sorokin A
Gutterman DD
Source :
Basic research in cardiology [Basic Res Cardiol] 2017 Jan; Vol. 112 (1), pp. 5. Date of Electronic Publication: 2016 Dec 19.
Publication Year :
2017

Abstract

In microvessels of patients with coronary artery disease (CAD), flow-mediated dilation (FMD) is largely dependent upon the endothelium-derived hyperpolarizing factor H <subscript>2</subscript> O <subscript>2</subscript> . The goal of this study is to examine the influence of age and presence or absence of disease on the mechanism of FMD. Human coronary or adipose arterioles (~150 µm diameter) were prepared for videomicroscopy. The effect of inhibiting COX [indomethacin (Indo) or NOS (L-NAME), eliminating H <subscript>2</subscript> O <subscript>2</subscript> (polyethylene glycol-catalase (PEG-CAT)] or targeting a reduction in mitochondrial ROS with scavengers/inhibitors [Vitamin E ( <subscript>mt</subscript> Vitamin E); phenylboronic acid ( <subscript>mt</subscript> PBA)] was determined in children aged 0-18 years; young adults 19-55 years; older adults >55 years without CAD, and similarly aged adults with CAD. Indo eliminated FMD in children and reduced FMD in younger adults. This response was mediated mainly by PGI <subscript>2</subscript> , as the prostacyclin-synthase-inhibitor trans-2-phenyl cyclopropylamine reduced FMD in children and young adults. L-NAME attenuated dilation in children and younger adults and eliminated FMD in older adults without CAD, but had no effect on vessels from those with CAD, where mitochondria-derived H <subscript>2</subscript> O <subscript>2</subscript> was the primary mediator. The magnitude of dilation was reduced in older compared to younger adults independent of CAD. Exogenous treatment with a sub-dilator dose of NO blocked FMD in vessels from subjects with CAD, while prolonged inhibition of NOS in young adults resulted in a phenotype similar to that observed in disease. The mediator of coronary arteriolar FMD evolves throughout life from prostacyclin in youth, to NO in adulthood. With the onset of CAD, NO-inhibitable release of H <subscript>2</subscript> O <subscript>2</subscript> emerges as the exclusive mediator of FMD. These findings have implications for use of pharmacological agents, such as nonsteroidal anti-inflammatory agents in children and the role of microvascular endothelium in cardiovascular health.

Details

Language :
English
ISSN :
1435-1803
Volume :
112
Issue :
1
Database :
MEDLINE
Journal :
Basic research in cardiology
Publication Type :
Academic Journal
Accession number :
27995364
Full Text :
https://doi.org/10.1007/s00395-016-0594-x