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生长激素、胰岛素样生长因子-1、胰岛素抵抗和白细胞端粒长度作为无心血管疾病受试者动脉衰老的决定因素。

Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases.

作者信息

Strazhesko Irina D, Tkacheva Olga N, Akasheva Dariga U, Dudinskaya Ekaterina N, Plokhova Ekaterina V, Pykhtina Valentina S, Kruglikova Anna S, Brailova Natalia V, Sharashkina Natalia V, Kashtanova Daria A, Isaykina Olesya Y, Pokrovskaya Mariya S, Vygodin Vladimir A, Ozerova Irina N, Skvortsov Dmitry A, Boytsov Sergey A

机构信息

Department of Clinical Cardiology and Molecular Genetics, Federal State Institution National Medical Research Center for Preventive Medicine of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.

Department of Age-associated Diseases, Medical Scientific and Educational Center, Lomonosov Moscow State University, Moscow, Russia.

出版信息

Front Genet. 2017 Dec 15;8:198. doi: 10.3389/fgene.2017.00198. eCollection 2017.

Abstract

Increased arterial stiffness (AS), intima-media thickness (IMT), and the presence of atherosclerotic plaques (PP) have been considered as important aspects of vascular aging. It is well documented that the cardiovascular system is an important target organ for growth hormone (GH) and insulin-like growth factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the risk for cardiovascular diseases (CVD). The telomere length of peripheral blood leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed as an independent predictor of (CVD). The aim of this study is to determine the role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in the vascular aging. The study group included 303 ambulatory participants free of known CVD (104 males and 199 females) with a mean age of 51.8 ± 13.3 years. All subjects had one or more CVRF [age, smoking, arterial hypertension, obesity, dyslipidemia, fasting hyperglycemia, insulin resistance-HOMA (homeostatic model assessment) >2.5, or high glycated hemoglobin]. The study sample was divided into the two groups according to age as "younger" ( ≤ 45 years, ≤ 55 years) and "older" ( > 45 years, > 55 years). IMT and PP were determined by ultrasonography, AS was determined by measuring the carotid-femoral pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL was determined by PCR. Serum IGF-1 and GH concentrations we measured by immunochemiluminescence analysis. Multiple linear regression analysis with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an independent relationship with all the arterial wall parameters investigated in the younger group. In the model with c-f PWV as a dependent variable, < 0.001 for HOMA, = 0.03 for GH, and = 0.004 for LTL. In the model with IMT as a dependent variable, = 0.0001 for HOMA, = 0.044 for GH, and = 0.004 for IGF-1. In the model with the number of plaques as a dependent variable, = 0.0001 for HOMA, and = 0.045 for IGF-1. In the older group, there were no independent significant associations between GH/IGF-1, LTL, HOMA, and arterial wall characteristics. GH/IGF-1, IR, HOMA, and LTL were the important parameters of arterial aging in younger healthy participants.

摘要

动脉僵硬度(AS)增加、内膜中层厚度(IMT)增加以及动脉粥样硬化斑块(PP)的存在被视为血管老化的重要方面。有充分文献记载,心血管系统是人类生长激素(GH)和胰岛素样生长因子(IGF)-1的重要靶器官,而GH/IGF-1缺乏会显著增加心血管疾病(CVD)的风险。外周血白细胞端粒长度(LTL)是细胞衰老的生物标志物,并已被提议作为CVD的独立预测指标。本研究的目的是确定GH/IGF-1、LTL及其相互作用在心血管危险因素(CVRF)对血管老化中的作用。研究组包括303名无已知CVD的门诊参与者(104名男性和199名女性),平均年龄为51.8±13.3岁。所有受试者都有一个或多个CVRF[年龄、吸烟、动脉高血压、肥胖、血脂异常、空腹血糖升高、胰岛素抵抗-HOMA(稳态模型评估)>2.5或高糖化血红蛋白]。研究样本根据年龄分为“较年轻”(≤45岁,≤55岁)和“较年长”(>45岁,>55岁)两组。IMT和PP通过超声检查确定,AS通过使用SphygmoCor系统(AtCor Medical)测量颈股脉搏波速度(c-f PWV)来确定。LTL通过聚合酶链反应确定。血清IGF-1和GH浓度通过免疫化学发光分析测量。对CVRF进行校正的多元线性回归分析表明,在较年轻组中,HOMA、GH、IGF-1和LTL与所有研究的动脉壁参数均存在独立关系。在以c-f PWV为因变量的模型中,HOMA的P<0.001,GH的P = 0.03,LTL的P = 0.004。在以IMT为因变量的模型中,HOMA的P = 0.0001,GH的P = 0.044,IGF-1的P = 0.004。在以斑块数量为因变量的模型中,HOMA的P = 0.0001,IGF-1的P = 0.045。在较年长组中,GH/IGF-1、LTL、HOMA与动脉壁特征之间不存在独立的显著关联。GH/IGF-1、胰岛素抵抗、HOMA和LTL是较年轻健康参与者动脉老化的重要参数。

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