Genetic predisposition to albuminuria is associated with increased arterial stiffness: role of elastin
Genetic predisposition to albuminuria is associated with increased arterial stiffness: role of elastin
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DOI：
10.1111/bph.13223
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发表时间：
2015-09-01
影响因子：
7.3
通讯作者：
Somoza, B.
中科院分区：
文献类型：
--
作者：
Gil-Ortega, M.;Garcia-Prieto, C. F.;Somoza, B.
背景和目的慕尼黑Wistar Fromter（MWF）大鼠是研究进行性白蛋白尿条件下心血管变化的实验模型。本研究的目的是评估蛋白尿的遗传易感性与动脉硬化和/或血管重塑的发展之间的关联。实验方法实验在来自12周龄MWF的肠系膜动脉中进行，Wistar京都（WKY）和consomic MWF-6（SHR）和MWF-8（SHR）其中来自MWF的与白蛋白尿相关的染色体6或8被来自自发性高血压大鼠（SHR）的相应染色体取代的大鼠。与WKY组相比，蛋白尿MWF组血管壁应力和应变降低，动脉僵硬度显著增加。与MWF相比，MWF-8（SHR）和MWF-6（SHR）的蛋白尿抑制与较低的-值相关。此外，弹性蛋白含量显着低于MWF外弹性膜相比，WKY和两个conomic应变。此外，与WKY相比，MWF中检测到动脉外径和内径以及横截面积减少，从而表现出向内的营养不良重塑。然而，这些变化保持不变，在两个consomic strains.Conclusion和ImplicationsThese数据表明，蛋白尿在MWF与动脉僵硬度增加，由于减少弹性蛋白含量的外部弹性膜。此外，MWF中的向内营养不良重构与蛋白尿没有直接关系。相反，我们发现两个主要的基因位点影响蛋白尿和动脉硬化的发展，从而将蛋白尿和阻力动脉机械性能的损伤联系起来。
Background and PurposeThe Munich Wistar Fromter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffness and/or vascular remodelling.Experimental ApproachExperiments were performed in mesenteric arteries from 12-week-old MWF, Wistar Kyoto (WKY) and consomic MWF-6(SHR) and MWF-8(SHR) rats in which chromosomes 6 or 8 associated with albuminuria from MWF were replaced by the respective chromosome from spontaneously hypertensive rats (SHR).Key ResultsIncremental distensibility, wall stress and strain were reduced, and arterial stiffness was significantly increased in albuminuric MWF compared with WKY. Albuminuria suppression in both consomic strains was associated with lower -values in MWF-8(SHR) and MWF-6(SHR) compared with MWF. Moreover, elastin content was significantly lower in MWF external elastic lamina compared with WKY and both consomic strains. In addition, a reduction in arterial external and internal diameter and cross-sectional area was detected in MWF compared with WKY, thus exhibiting an inward hypotrophic remodelling. However, these alterations remained unchanged in both consomic strains.Conclusion and ImplicationsThese data demonstrate that albuminuria in MWF is associated with increased arterial stiffness due to a reduction of elastin content in the external elastic lamina. Moreover, inward hypotrophic remodelling in MWF is not directly associated with albuminuria. In contrast, we demonstrated that two major genetic loci affect both the development of albuminuria and arterial stiffness, thus linking albuminuria and impairment of mechanical properties of resistance arteries.