Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Labnet Laboratories, Department of Molecular Biology and Genetics, 54638 Thessaloniki, Greece.
Cells. 2022 Feb 10;11(4):607. doi: 10.3390/cells11040607.
MicroRNAs (miRNAs) create systems networks and gene-expression circuits through molecular signaling and cell interactions that contribute to health imbalance and the emergence of cardiovascular disorders (CVDs). Because the clinical phenotypes of CVD patients present a diversity in their pathophysiology and heterogeneity at the molecular level, it is essential to establish genomic signatures to delineate multifactorial correlations, and to unveil the variability seen in therapeutic intervention outcomes. The clinically validated miRNA biomarkers, along with the relevant SNPs identified, have to be suitably implemented in the clinical setting in order to enhance patient stratification capacity, to contribute to a better understanding of the underlying pathophysiological mechanisms, to guide the selection of innovative therapeutic schemes, and to identify innovative drugs and delivery systems. In this article, the miRNA-gene networks and the genomic signatures resulting from the SNPs will be analyzed as a method of highlighting specific gene-signaling circuits as sources of molecular knowledge which is relevant to CVDs. In concordance with this concept, and as a case study, the design of the clinical trial GESS (NCT03150680) is referenced. The latter is presented in a manner to provide a direction for the improvement of the implementation of pharmacogenomics and precision cardiovascular medicine trials.
微小 RNA（miRNA）通过分子信号和细胞相互作用构建系统网络和基因表达回路，从而导致健康失衡和心血管疾病（CVD）的发生。由于 CVD 患者的临床表型在病理生理学上存在多样性，在分子水平上存在异质性，因此建立基因组特征以描绘多因素相关性并揭示治疗干预结果中的可变性至关重要。临床验证的 miRNA 生物标志物以及确定的相关 SNP 必须在临床环境中得到适当实施，以增强患者分层能力，有助于更好地理解潜在的病理生理机制，指导创新治疗方案的选择，并确定创新药物和输送系统。在本文中，将分析 miRNA-基因网络和 SNP 产生的基因组特征，作为突出特定基因信号通路的方法，这些信号通路是与 CVD 相关的分子知识的来源。根据这一概念，作为案例研究，参考了临床试验 GESS（NCT03150680）的设计。以提供改善药物基因组学和精准心血管医学试验实施方向的方式呈现后者。
