Aortic and carotid arterial stiffness and epigenetic regulator gene expression changes precede blood pressure rise in stroke-prone Dahl salt-sensitive hypertensive rats.
Aortic and carotid arterial stiffness and epigenetic regulator gene expression changes precede blood pressure rise in stroke-prone Dahl salt-sensitive hypertensive rats.
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DOI：
10.1371/journal.pone.0107888
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ruiz-Opazo N
中科院分区：
文献类型：
--
作者：
Herrera VL;Decano JL;Giordano N;Moran AM;Ruiz-Opazo N
多项临床研究表明，以脉搏波速度（PWV）测量的动脉硬度先于高血压，是高血压末端器官疾病（包括中风、心血管疾病和慢性肾脏疾病）的独立预测因子。动脉僵硬的危险因素包括年龄、高血压和钠。然而，将危险因素与动脉硬化联系起来的因果机制仍有待阐明。在此，我们在na诱导的卒中易发的Dahl盐敏感(S)高血压大鼠模型中研究了动脉僵硬与高血压的因果关系，并分析了可能的分子机制。在3周龄和6周龄时，研究了卒中易发和非卒中易发的雄性和雌性大鼠的动脉硬度（PWV、应变）、血压、血管壁组织学和基因表达变化。研究表明，在6周时间点，左颈动脉和主动脉僵硬度增加先于高血压、脉压增宽和结构壁改变。相反，差异基因诱导被检测到涉及细胞外基质（ECM）结构成分、修饰剂、细胞粘附和基质细胞蛋白的分子功能变化，以及内皮功能、细胞凋亡平衡和表观遗传调节因子。免疫染色检测组蛋白修饰剂Ep300、HDAC3和PRMT5水平证实了颈动脉内皮细胞、平滑肌细胞和外膜细胞三层均上调。我们的研究总结了在人类中观察到的盐敏感性，在高血压，脉压升高和血管壁结构改变之前，钠摄入量增加会引起动脉僵硬。与动脉僵硬相关的差异基因表达变化提示了一种分子机制，将钠与影响血管ECM结构-功能、细胞凋亡平衡和表观遗传调控相关的基因网络联系起来。
Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S) hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain), blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM) structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.
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影响因子：
37.8
作者：
Fujiwara, N;Osanai, T;Okumura, K
通讯作者：
Okumura, K
影响因子：
3.1
作者：
Decano, Julius L.;Moran, Anne Marie;Ruiz-Opazo, Nelson;Herrera, Victoria L. M.
通讯作者：
Herrera, Victoria L. M.
DOI：
10.1161/01.atv.6.2.166
发表时间：
1986-03-01
期刊：
ARTERIOSCLEROSIS
影响因子：
--
作者：
AVOLIO, AP;CLYDE, KM;OROURKE, MF
通讯作者：
OROURKE, MF
影响因子：
4.6
作者：
Herrera, Victoria L. M.;Tsikoudakis, Aristides;Ruiz-Opazo, Nelson
通讯作者：
Ruiz-Opazo, Nelson
影响因子：
8.3
作者：
CHRISTENSEN, KL
通讯作者：
CHRISTENSEN, KL