Elevated sodium and dehydration stimulate inflammatory signaling in endothelial cells and promote atherosclerosis.
Elevated sodium and dehydration stimulate inflammatory signaling in endothelial cells and promote atherosclerosis.
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DOI：
10.1371/journal.pone.0128870
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Burg MB
中科院分区：
文献类型：
--
作者：
Dmitrieva NI;Burg MB
心血管疾病（cvd）是世界范围内的主要健康问题。流行病学研究将高盐摄入量和易脱水的情况（如低水摄入量、糖尿病和老年）与心血管疾病的风险增加联系起来。先前，我们证明了细胞外钠的升高，这是这些疾病的常见后果，刺激内皮细胞产生凝血引发因子，血管性血液病因子，增加其在血液中的水平，促进血栓形成。本研究以人脐静脉内皮细胞（HUVECs）为研究对象，采用PCR技术，分析了高NaCl对内皮细胞生物学相关基因84个的影响。分析表明，受影响的基因调控内皮细胞生物学的许多方面，包括细胞粘附、增殖、白细胞和淋巴细胞活化、凝血、血管生成和炎症反应。表达增加最多的基因是黏附分子VCAM1和e -选择素以及趋化剂MCP-1。它们是白细胞粘附和转运的关键参与者，在心血管疾病（包括动脉粥样硬化）的炎症和病理生理中发挥重要作用。事实上，高NaCl增加了单核细胞的粘附和它们通过HUVECs单层的迁移。小鼠轻度限水可使血清钠升高5 mmol/l，增加小鼠组织中VCAM1、e -选择素和MCP-1的表达，加速主动脉根部动脉粥样硬化斑块形成，引起冠状动脉壁增厚。社区动脉粥样硬化风险研究（n=12779）临床数据的多变量线性回归分析表明，血清钠是10年冠心病风险的重要预测因子。这些发现表明，细胞外钠在生理范围内的升高伴随着血管的变化，从而促进心血管疾病的发展。研究结果引起了人们对血清钠作为心血管疾病危险因素的关注，并为饮食盐限制和充足的水摄入作为预防心血管疾病的建议提供了额外的支持。
Cardiovascular diseases (CVDs) are a leading health problem worldwide. Epidemiologic studies link high salt intake and conditions predisposing to dehydration such as low water intake, diabetes and old age to increased risk of CVD. Previously, we demonstrated that elevation of extracellular sodium, which is a common consequence of these conditions, stimulates production by endothelial cells of clotting initiator, von Willebrand Factor, increases its level in blood and promotes thrombogenesis. In present study, by PCR array, using human umbilical vein endothelial cells (HUVECs), we analyzed the effect of high NaCl on 84 genes related to endothelial cell biology. The analysis showed that the affected genes regulate many aspects of endothelial cell biology including cell adhesion, proliferation, leukocyte and lymphocyte activation, coagulation, angiogenesis and inflammatory response. The genes whose expression increased the most were adhesion molecules VCAM1 and E-selectin and the chemoattractant MCP-1. These are key participants in the leukocyte adhesion and transmigration that play a major role in the inflammation and pathophysiology of CVD, including atherosclerosis. Indeed, high NaCl increased adhesion of mononuclear cells and their transmigration through HUVECs monolayers. In mice, mild water restriction that elevates serum sodium by 5 mmol/l, increased VCAM1, E-selectin and MCP-1 expression in mouse tissues, accelerated atherosclerotic plaque formation in aortic root and caused thickening or walls of coronary arteries. Multivariable linear regression analysis of clinical data from the Atherosclerosis Risk in Communities Study (n=12779) demonstrated that serum sodium is a significant predictor of 10 Years Risk of coronary heart disease. These findings indicate that elevation of extracellular sodium within the physiological range is accompanied by vascular changes that facilitate development of CVD. The findings bring attention to serum sodium as a risk factor for CVDs and give additional support to recommendations for dietary salt restriction and adequate water intake as preventives of CVD.
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影响因子：
3.2
作者：
Croce, Kevin;Libby, Peter
通讯作者：
Libby, Peter
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影响因子：
12.3
作者：
Huang, Da Wei;Sherman, Brad T;Tan, Qina;Collins, Jack R;Alvord, W Gregory;Roayaei, Jean;Stephens, Robert;Baseler, Michael W;Lane, H Clifford;Lempicki, Richard A
通讯作者：
Lempicki, Richard A
影响因子：
4.3
作者：
Dmitrieva, Natalia I.;Burg, Maurice B.
通讯作者：
Burg, Maurice B.
DOI：
10.1073/pnas.0403139101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Go, WY;Liu, XB;Ho, SN
通讯作者：
Ho, SN
影响因子：
64.8
作者：
Boring, L;Gosling, J;Charo, IF
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