Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.
Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.
复制标题
DAHL盐敏感高血压大鼠的动脉刚度的性别特异性遗传决定因素。
DOI：
10.1186/s12863-015-0324-7
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发表时间：
2016-01-11
期刊：
影响因子：
2.9
通讯作者：
Ruiz-Opazo N
中科院分区：
文献类型：
--
作者：
Decano JL;Pasion KA;Black N;Giordano NJ;Herrera VL;Ruiz-Opazo N
动脉僵硬度是高血压患者心血管结局的独立预测因子，包括心肌梗死、致死性卒中、脑微出血（可预测高血压患者的脑出血）以及非高血压受试者进展为高血压。在调整年龄、性别、血压、体重指数和其他已知的心血管疾病预测因素后，动脉僵硬度与各种心血管结局（冠心病、中风）之间的相关性仍然存在，这表明通过颈动脉-股动脉脉搏波速度测量的动脉僵硬度比这些因素中的每一个都具有更好的预测价值。最近的证据表明，动脉硬化先于高血压的发病;然而，它们的分子遗传关系和性别特异性决定因素仍然不确定。我们调查了不同或共享的遗传决定因素是否可能导致雄性和雌性达尔盐敏感大鼠动脉硬化的易感性。因此，我们进行了全基因组扫描的数量性状基因座（QTL）影响动脉硬度在6周龄F2（达尔S × R）-intercross雄性和雌性大鼠的特点是腹主动脉脉搏波速度和主动脉应变的高分辨率超声。我们检测到5个影响主动脉僵硬度的高度显著的QTL：男性中的两个相互作用的QTL（4号染色体上的AS-m1和16号染色体上的AS-m2，LOD 8.8）和女性中影响脉搏波速度的两个不同的相互作用的QTL（9号染色体上的AS-f1和11号染色体上的AS-f2，LOD 8.9）。发现一个QTL（3号染色体上的AS-1，LOD 4.3）以不依赖性别的方式影响主动脉应变。这些动脉僵硬度QTL没有一个与以前报道的血压QTL在等价的遗传互交中检测到的共定位。这些数据揭示了主动脉脉搏波速度的性别特异性遗传决定因素，并表明Dahl大鼠动脉僵硬和盐敏感性高血压的不同多基因易感性，基于报道的血压QTL在等效（Dahl S x R）-intercrosses。
Arterial stiffness is an independent predictor of cardiovascular outcomes in hypertensive patients including myocardial infarction, fatal stroke, cerebral micro-bleeds which predicts cerebral hemorrhage in hypertensive patients, as well as progression to hypertension in non-hypertensive subjects. The association between arterial stiffness and various cardiovascular outcomes (coronary heart disease, stroke) remains after adjusting for age, sex, blood pressure, body mass index and other known predictors of cardiovascular disease, suggesting that arterial stiffness, measured via carotid-femoral pulse wave velocity, has a better predictive value than each of these factors. Recent evidence shows that arterial stiffening precedes the onset of high blood pressure; however their molecular genetic relationship (s) and sex-specific determinants remain uncertain. We investigated whether distinct or shared genetic determinants might underlie susceptibility to arterial stiffening in male and female Dahl salt-sensitive rats. Thus, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting arterial stiffness in six-week old F2 (Dahl S x R)-intercross male and female rats characterized for abdominal aortic pulse wave velocity and aortic strain by high-resolution ultrasonography. We detected five highly significant QTLs affecting aortic stiffness: two interacting QTLs (AS-m1 on chromosome 4 and AS-m2 on chromosome16, LOD 8.8) in males and two distinct interacting QTLs (AS-f1 on chromosome 9 and AS-f2 on chromosome11, LOD 8.9) in females affecting pulse wave velocity. One QTL (AS-1 on chromosome 3, LOD 4.3) was found to influence aortic strain in a sex-independent manner. None of these arterial stiffness QTLs co-localized with previously reported blood pressure QTLs detected in equivalent genetic intercrosses. These data reveal sex-specific genetic determinants for aortic pulse wave velocity and suggest distinct polygenic susceptibility for arterial stiffness and salt-sensitive hypertension in Dahl rats based upon reported blood pressure QTLs in equivalent (Dahl S x R)-intercrosses.