J Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension
J Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension
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DOI：
10.1111/bph.13457
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发表时间：
2016-05-01
影响因子：
7.3
通讯作者：
Briones, A. M.
中科院分区：
文献类型：
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作者：
Avendano, M. S.;Martinez-Revelles, S.;Briones, A. M.
背景和目的考克斯-2和EP受体衍生的前列腺素参与不同心血管疾病的血管重构。本研究旨在探讨考克斯-2和EP-1受体在高血压血管重构和功能中的作用。实验方法：（1.44 mg kg（-1）天（-1），2周）小鼠接受考克斯-2抑制剂塞来昔布（25 mgkg（-1）天（-1）腹腔注射）或EP 1受体拮抗剂SC 19220（10 mgkg（-1）天（-1）腹腔注射）治疗。考克斯-2（-/-）小鼠或无血管紧张素II infusion were also used.Key ResultsCelecoxib和SC 19220治疗没有修改改变管腔直径和壁：管腔比从SHR灌注和/或血管紧张素II灌注动物肠系膜阻力动脉。然而，这两种治疗和考克斯-2缺陷降低了血管的血管硬度增加高血压动物。这是伴随着减少血管胶原沉积，正常化改变弹性蛋白结构和减少结缔组织生长因子和纤溶酶原激活物抑制剂-1基因表达。考克斯-2缺陷和SC 19220治疗减少了血管收缩反应和血管紧张素II输注诱导的内皮功能障碍。高血压动物显示血管组织中mPGES-1表达和PGE（2）产生增加，塞来昔布使其正常化。塞来昔布治疗还降低了AngII诱导的巨噬细胞浸润和TNF-α表达。巨噬细胞条件培养基（MCM）增加血管平滑肌细胞中考克斯-2和I型胶原的表达;后者被塞来昔布治疗降低。结论和意义考克斯-2和EP 1受体参与细胞外基质沉积增加和血管僵硬，血管功能受损和炎症在高血压。靶向PGE（2）受体可能对高血压相关的血管损伤有益。
Background and PurposeProstanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension.Experimental ApproachSpontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mgkg(-1)day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mgkg(-1)day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mgkg(-1)day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used.Key ResultsCelecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR-infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE(2) production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF- expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment.Conclusions and ImplicationsCOX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE(2) receptors might have benefits in hypertension-associated vascular damage.