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部分胰岛素样生长因子-1缺乏足以降低心脏收缩性、血管紧张素II敏感性,并改变心脏结构和功能蛋白的基因表达。

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

作者信息

González-Guerra José Luis, Castilla-Cortazar Inma, Aguirre Gabriel A, Muñoz Úrsula, Martín-Estal Irene, Ávila-Gallego Elena, Granado Miriam, Puche Juan E, García-Villalón Ángel Luis

机构信息

Escuela de Medicina, Tecnológico de Monterrey, Monterrey, México.

Fundación de Investigación Hospitales de Madrid, HM Hospitales, Madrid, Spain.

出版信息

PLoS One. 2017 Aug 14;12(8):e0181760. doi: 10.1371/journal.pone.0181760. eCollection 2017.

Abstract

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

摘要

在衰老、代谢综合征和晚期肝硬化等多种情况下,循环中的胰岛素样生长因子-1(IGF-1)水平可能会降低。这种降低与胰岛素抵抗、血脂异常、进展为2型糖尿病以及心血管疾病风险增加有关。然而,IGF-1缺乏与心血管疾病之间的潜在机制仍不清楚。本研究的具体目的是通过比较缺血再灌注(I/R)前后的血管活性因子,研究部分IGF-1缺乏是否会影响心脏和/或冠状动脉循环。此外,还对心脏进行了组织学检查,并检测了参与心脏结构和功能的蛋白质(细胞外基质、收缩蛋白、活性肽)的基因表达;采用微阵列进行检测,随后通过RT-qPCR对三个实验组进行确认。IGF-1部分缺乏与心肌收缩力和血管紧张素II敏感性降低、间质纤维化以及参与细胞外基质蛋白、钙动力学和心脏结构与功能的基因表达模式改变有关。尽管本研究是描述性的,但它清楚地揭示了部分IGF-1缺乏对心脏的影响,并将该实验模型确立为适合研究心脏病机制和探索IGF-1缺乏患者治疗方案的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4599/5555709/462d547021c1/pone.0181760.g001.jpg

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