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Cystathionine γ-Lyase Modulates Flow-Dependent Vascular Remodeling.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2018 Sep; Vol. 38 (9), pp. 2126-2136. - Publication Year :
- 2018
-
Abstract
- Objective- Flow patterns differentially regulate endothelial cell phenotype, with laminar flow promoting vasodilation and disturbed flow promoting endothelial proinflammatory activation. CSE (cystathionine γ-lyase), a major source of hydrogen sulfide (H <subscript>2</subscript> S) in endothelial cells, critically regulates cardiovascular function, by both promoting vasodilation and reducing endothelial activation. Therefore, we sought to investigate the role of CSE in the endothelial response to flow. Approach and Results- Wild-type C57Bl/6J and CSE knockout ( CSE <superscript>-/-</superscript> ) mice underwent partial carotid ligation to induce disturbed flow in the left carotid. In addition, endothelial cells isolated from wild-type and CSE <superscript>-/-</superscript> mice were exposed to either laminar or oscillatory flow, an in vitro model of disturbed flow. Interestingly, laminar flow significantly reduced CSE expression in vitro, and only disturbed flow regions show discernable CSE protein expression in vivo, correlating with enhanced H <subscript>2</subscript> S production in wild-type C57BL/6J but not CSE <superscript>-/-</superscript> mice. Lack of CSE limited disturbed flow-induced proinflammatory gene expression (ICAM-1[intercellular adhesion molecule 1], VCAM-1 [vascular cell adhesion molecular 1]) and monocyte infiltration and CSE <superscript>-/-</superscript> endothelial cells showed reduced NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and proinflammatory gene expression in response to oscillatory flow in vitro. In addition, CSE <superscript>-/-</superscript> mice showed reduced inward remodeling after partial carotid ligation. CSE <superscript>-/-</superscript> mice showed elevated vascular nitrite levels (measure of nitric oxide [NO]) in the unligated carotids, suggesting an elevation in baseline NO production, and the NO scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide normalized the reduced inward remodeling, but not inflammation, of ligated carotids in CSE <superscript>-/-</superscript> mice. Conclusions- CSE expression in disturbed flow regions critically regulates both endothelial activation and flow-dependent vascular remodeling, in part through altered NO availability.
- Subjects :
- Animals
Benzoates metabolism
Biological Availability
Carotid Arteries physiology
Cells, Cultured
Cystathionine gamma-Lyase genetics
Gene Expression
Humans
Hydrogen Sulfide metabolism
Imidazoles metabolism
Inflammation physiopathology
Intercellular Adhesion Molecule-1 genetics
Intercellular Adhesion Molecule-1 metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Monocytes metabolism
NF-kappa B metabolism
Nitric Oxide metabolism
Signal Transduction
Stress, Mechanical
Vascular Cell Adhesion Molecule-1 genetics
Vascular Cell Adhesion Molecule-1 metabolism
Vasodilation
Blood Flow Velocity
Cystathionine gamma-Lyase metabolism
Endothelial Cells physiology
Vascular Remodeling physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 38
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 30002061
- Full Text :
- https://doi.org/10.1161/ATVBAHA.118.311402