5-Lipoxagenase deficiency attenuates L-NAME-induced hypertension and vascular remodeling
| Autor: | Ruli Li, Caili Zhuo, Kunyue Xue, He Li, Wei Jiang, Xin Yan, Juanjuan Xin, Xu-Lei Wang, Xue Li, Jie Lan, Xiao-Xiao Wang, Heng-Yu Zhang, Ling-yu Li, Zi-jie Deng, Jia-Xiang Chen, Lu Gan, Ming-ming Tong |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Vascular smooth muscle Neutrophils Leukotriene B4 Nitric Oxide Synthase Type II Blood Pressure Vascular Remodeling 030204 cardiovascular system & hematology Muscle Smooth Vascular Rats Sprague-Dawley Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Cell Movement Internal medicine medicine Animals Molecular Biology Aorta Cell Proliferation Mice Knockout Arachidonate 5-Lipoxygenase biology Chemistry Colocalization Leukotriene A4 Rats Mice Inbred C57BL NG-Nitroarginine Methyl Ester 030104 developmental biology Endocrinology Blood pressure Hypertension Arachidonate 5-lipoxygenase biology.protein Molecular Medicine Immunohistochemistry Elastin |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1865:2379-2392 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2019.05.021 |
| Popis: | Background Abnormalities of the L-arginine-nitric oxide pathway induce hypertension. 5-Lipoxygenase (5-LO) is the key enzyme involved in synthesis of leukotrienes (LTs). However, whether nitricoxide synthase dysfunction induces hypertensive vascular remodeling by regulating 5-LO activity and its downstream inflammatory metabolites remains unknown. Methods and results Six-week L-NAME treatment significantly induced hypertension and vascular remodeling in both wild-type (WT) and 5-LO–knockout (5-LO–KO) mice, and blood pressure in caudal and carotid arteries was lower in 5-LO–KO than WT mice with L-NAME exposure. On histology, L-NAME induced less media thickness, media-to-lumen ratio, and collagen deposition and fewer Ki-67–positive vascular smooth muscle cells (VSMCs) but more elastin expression in thoracic and mesenteric aortas of 5-LO–KO than L-NAME–treated WT mice. L-NAME significantly increased LT content, including LTB4 and cysteinyl LT (CysLTs), in plasma and neutrophil culture supernatants from WT mice. On immunohistochemistry, L-NAME promoted the colocalization of 5-LO and 5-LO–activating protein on the nuclear envelope of cultured neutrophils, which was accompanied by elevated LT content in culture supernatants. In addition, LTs significantly promoted BrdU incorporation, migration and phenotypic modulation in VSMCs. Conclusion L-NAME may activate the 5-LO/LT pathway in immune cells, such as neutrophils, and promote the products of 5-LO metabolites, including LTB4 and CysLTs, which aggravate vascular remodeling in hypertension. 5-LO deficiency may protect against hypertension and vascular remodeling by reducing levels of 5-LO downstream inflammatory metabolites. |
| Databáze: | OpenAIRE |
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