Yundung Yankey, Mohammed Shafeeq, Paneni Francesco, Reutersberg Benedikt, Rössler Fabian, Zimmermann Alexander, Pelisek Jaroslav
Experimental Vascular Surgery/Department of Vascular Surgery, University Hospital Zurich/University of Zurich, Schlieren, Switzerland.
Department of Cardiology/Center for Translational and Experimental Cardiology (CTEC), University Hospital Zurich/University of Zurich, Schlieren, Switzerland.
Sci Rep. 2024 Apr 14;14(1):8615. doi: 10.1038/s41598-024-59164-7.
Diabetes mellitus (DM) is a significant risk factor for peripheral arterial disease (PAD), and PAD is an independent predictor of cardiovascular disorders (CVDs). Growing evidence suggests that long non-coding RNAs (lncRNAs) significantly contribute to disease development and underlying complications, particularly affecting smooth muscle cells (SMCs). So far, no study has focused on transcriptome analysis of lncRNAs in PAD patients with and without DM. Tissue samples were obtained from our Vascular Biobank. Due to the sample's heterogeneity, expression analysis of lncRNAs in whole tissue detected only ACTA2-AS1 with a 4.9-fold increase in PAD patients with DM. In contrast, transcriptomics of SMCs revealed 28 lncRNAs significantly differentially expressed between PAD with and without DM (FDR < 0.1). Sixteen lncRNAs were of unknown function, six were described in cancer, one connected with macrophages polarisation, and four were associated with CVDs, mainly with SMC function and phenotypic switch (NEAT1, MIR100HG, HIF1A-AS3, and MRI29B2CHG). The enrichment analysis detected additional lncRNAs H19, CARMN, FTX, and MEG3 linked with DM. Our study revealed several lncRNAs in diabetic PAD patients associated with the physiological function of SMCs. These lncRNAs might serve as potential therapeutic targets to improve the function of SMCs within the diseased tissue and, thus, the clinical outcome.
糖尿病（DM）是外周动脉疾病（PAD）的一个重要危险因素，而PAD是心血管疾病（CVD）的独立预测因子。越来越多的证据表明，长链非编码RNA（lncRNA）对疾病发展和潜在并发症有显著影响，尤其影响平滑肌细胞（SMC）。到目前为止，尚无研究聚焦于合并或未合并DM的PAD患者中lncRNA的转录组分析。组织样本取自我们的血管生物样本库。由于样本的异质性，全组织中lncRNA的表达分析仅检测到ACTA2-AS1，在合并DM的PAD患者中其表达增加了4.9倍。相比之下，SMC的转录组学显示，合并和未合并DM的PAD患者之间有28种lncRNA存在显著差异表达（错误发现率<0.1）。16种lncRNA功能未知，6种在癌症中有所描述，1种与巨噬细胞极化有关，4种与CVD有关，主要与SMC功能和表型转换有关（NEAT1、MIR100HG、HIF1A-AS3和MRI29B2CHG）。富集分析检测到另外几种与DM相关的lncRNA，即H19、CARMN、FTX和MEG3。我们的研究揭示了糖尿病PAD患者中几种与SMC生理功能相关的lncRNA。这些lncRNA可能作为潜在的治疗靶点，以改善病变组织中SMC的功能，从而改善临床结局。
