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Cystathionine γ-Lyase Modulates Flow-Dependent Vascular Remodeling
Shuai Yuan1, Arif Yurdagul1, Jonette M Peretik2
1From the Department of Cellular Biology and Anatomy (S.Y., A.Y., C.G.K., A.W.O.).
Arteriosclerosis, Thrombosis, and Vascular Biology
|July 14, 2018
Summary
Cystathionine γ-lyase (CSE) in disturbed blood flow regulates endothelial activation and vascular remodeling. Lack of CSE reduces inflammation and alters nitric oxide (NO) availability, impacting cardiovascular function.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Biology
- Mechanobiology
Background:
- Blood flow patterns critically influence endothelial cell phenotype, with laminar flow promoting vasodilation and disturbed flow inducing proinflammatory activation.
- Cystathionine γ-lyase (CSE) is a key enzyme producing hydrogen sulfide (H2S) in endothelial cells, regulating cardiovascular function by promoting vasodilation and reducing inflammation.
Purpose of the Study:
- To investigate the role of CSE in the endothelial response to different blood flow patterns.
- To determine how CSE influences endothelial activation, inflammation, and vascular remodeling under disturbed flow conditions.
Main Methods:
- Utilized a partial carotid ligation mouse model to induce disturbed flow in vivo.
- Exposed primary endothelial cells from wild-type and CSE knockout (CSE-/-) mice to laminar and oscillatory flow in vitro.
- Assessed CSE expression, H2S production, proinflammatory gene expression (ICAM-1, VCAM-1), monocyte infiltration, NF-κB activation, and vascular remodeling.
Main Results:
- Disturbed flow, but not laminar flow, induced CSE expression and H2S production in wild-type mice.
- CSE deficiency attenuated disturbed flow-induced proinflammatory gene expression, monocyte infiltration, and NF-κB activation.
- CSE-/- mice exhibited reduced inward vascular remodeling and elevated baseline nitric oxide (NO) levels.
Conclusions:
- CSE expression in disturbed flow regions is crucial for regulating endothelial activation and flow-dependent vascular remodeling.
- CSE influences vascular remodeling partly through modulation of NO availability.
- Targeting CSE may offer therapeutic strategies for cardiovascular diseases associated with disturbed flow.
Keywords:
cystathionine gamma-lyasedisturbed flowendothelial cellshydrogen sulfideshear stressvascular remodelingvasodilationMore Related Videos
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