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由 miR-15b 和 miR-29a 组成的网络参与老年缺血性心肌病患者胸腺脂肪组织中血管内皮生长因子通路的调节。

A Network Comprised of miR-15b and miR-29a Is Involved in Vascular Endothelial Growth Factor Pathway Regulation in Thymus Adipose Tissue from Elderly Ischemic Cardiomyopathy Subjects.

机构信息

Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29580 Malaga, Spain.

Clinical Unit of Endocrinology and Nutrition, University Regional Hospital of Malaga, 29009 Malaga, Spain.

出版信息

Int J Mol Sci. 2023 Sep 22;24(19):14456. doi: 10.3390/ijms241914456.

Abstract

As the human thymus ages, it undergoes a transformation into adipose tissue known as TAT. Interestingly, in previous research, we observed elevated levels of vascular endothelial growth factor A (VEGFA) in TAT from patients with ischemic cardiomyopathy (IC), particularly in those over 70 years old. Moreover, in contrast to subcutaneous adipose tissue (SAT), TAT in elderly individuals exhibits enhanced angiogenic properties and the ability to stimulate tube formation. This makes TAT a promising candidate for angiogenic therapies and the regeneration of ischemic tissues following coronary surgery. MicroRNAs (miRNAs) have emerged as attractive therapeutic targets, especially those that regulate angiogenic processes. The study's purpose is to determine the miRNA network associated with both the VEGFA pathway regulation and the enrichment of age-linked angiogenesis in the TAT. RT-PCR was used to analyze angiogenic miRNAs and the expression levels of their predicted target genes in both TAT and SAT from elderly and middle-aged patients treated with coronary artery bypass graft surgery. miRTargetLink Human was used to search for miRNAs and their target genes. PANTHER was used to annotate the biological processes of the predicted targets. The expression of miR-15b-5p and miR-29a-3p was significantly upregulated in the TAT of elderly compared with middle-aged patients. Interestingly, and other angiogenic targets were significantly upregulated in the TAT of elderly patients. Specifically: , , , , , , , , , and were upregulated, while and were downregulated. Our results provide strong evidence of a miRNA/mRNA interaction network linked with age-associated TAT angiogenic enrichment in patients with IC.

摘要

随着人体胸腺的衰老,它会转变为一种称为 TAT 的脂肪组织。有趣的是,在之前的研究中,我们观察到缺血性心肌病 (IC) 患者的 TAT 中血管内皮生长因子 A (VEGFA) 水平升高,尤其是 70 岁以上的患者。此外,与皮下脂肪组织 (SAT) 相比,老年个体的 TAT 具有增强的血管生成特性和刺激管形成的能力。这使得 TAT 成为血管生成治疗和冠状动脉手术后缺血组织再生的有前途的候选物。 microRNAs (miRNAs) 已成为有吸引力的治疗靶点,特别是那些调节血管生成过程的 miRNA。本研究旨在确定与 VEGFA 途径调节和 TAT 中与年龄相关的血管生成富集相关的 miRNA 网络。使用 RT-PCR 分析了接受冠状动脉旁路移植术治疗的老年和中年患者的 TAT 和 SAT 中的血管生成 miRNA 及其预测靶基因的表达水平。使用 miRTargetLink Human 搜索 miRNA 及其靶基因。使用 PANTHER 对预测靶基因的生物学过程进行注释。与中年患者相比,老年患者的 TAT 中 miR-15b-5p 和 miR-29a-3p 的表达明显上调。有趣的是,TAT 中许多其他血管生成靶基因的表达也明显上调。具体而言: 、 、 、 、 、 、 、 和 上调,而 下调。我们的结果提供了强有力的证据,证明 miRNA/mRNA 相互作用网络与 IC 患者 TAT 中与年龄相关的血管生成富集有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/764c/10572810/4996a87f9eba/ijms-24-14456-g001.jpg

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