Cystathionine -Lyase Modulates Flow-Dependent Vascular Remodeling

被引：46

作者：

Yuan, Shuai ^{[1
]}

Yurdagul, Arif, Jr. ^{[1
]}

Peretik, Jonette M. ^{[2
]}

Alfaidi, Mabruka ^{[2
]}

Al Yafeai, Zaki ^{[3
]}

Pardue, Sibile ^{[2
]}

Kevil, Christopher G. ^{[1
,2
,3
,4
]}

Orr, A. Wayne ^{[1
,2
,3
,4
]}

机构：

[1] Louisiana State Univ, Hlth Sci Ctr, Dept Cellular Biol & Anat, Shreveport, LA 71105 USA

[2] Louisiana State Univ, Hlth Sci Ctr, Dept Pathol & Translat Pathobiol, Shreveport, LA 71105 USA

[3] Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71105 USA

[4] Louisiana State Univ, Hlth Sci Ctr, Ctr Cardiovasc Dis & Sci, Shreveport, LA 71105 USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2018年 / 38卷 / 09期

基金：

美国国家卫生研究院;

关键词：

cystathionine gamma-lyase; disturbed flow; endothelial cells; hydrogen sulfide; shear stress; vascular remodeling; vasodilation; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; E KNOCKOUT MICE; HYDROGEN-SULFIDE; GAMMA-LYASE; ENDOTHELIAL FUNCTION; DISTURBED FLOW; IN-VIVO; ACTIVATION; ATHEROSCLEROSIS;

D O I：

10.1161/ATVBAHA.118.311402

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective Flow patterns differentially regulate endothelial cell phenotype, with laminar flow promoting vasodilation and disturbed flow promoting endothelial proinflammatory activation. CSE (cystathionine -lyase), a major source of hydrogen sulfide (H2S) 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-/-) mice underwent partial carotid ligation to induce disturbed flow in the left carotid. In addition, endothelial cells isolated from wild-type and CSE-/- 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 H2S production in wild-type C57BL/6J but not CSE-/- 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-/- endothelial cells showed reduced NF-B (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-/- mice showed reduced inward remodeling after partial carotid ligation. CSE-/- 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-/- mice. Conclusions CSE expression in disturbed flow regions critically regulates both endothelial activation and flow-dependent vascular remodeling, in part through altered NO availability.

引用

页码：2126 / 2136

页数：11

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