Abstract:
Atherosclerotic disease is a major cause of morbidity and mortality worldwide. Atherosclerosis may be present in different arterial territories and as a single- or multi-territorial disease. The different phenotypes of atherosclerosis are attributable only in part to acquired cardiovascular risk factors and genetic Mendelian inheritance. miRNAs, which regulate the gene expression at the post-transcriptional level, may also contribute to such heterogeneity. Numerous miRNAs participate in the pathophysiology of atherosclerosis by modulating endothelial function, smooth vascular cell function, vascular inflammation, and cholesterol homeostasis in the vessel, among other biological processes. Moreover, miRNAs are present in peripheral blood with high stability and have the potential to be used as non-invasive biomarkers for the diagnosis of atherosclerosis. However, the circulating miRNA profile may vary according to the involved arterial territory, considering that atherosclerosis expression, including the associated molecular phenotype, varies according to the affected arterial territory. In this review, we discuss the specific circulating miRNA profiles associated with atherosclerosis of different arterial territories, the common circulating miRNA profile of stable atherosclerosis irrespective of the involved arterial territory, and the circulating miRNA signature of multi-territorial atherosclerosis. miRNAs may consist of a simple non-invasive method for discriminating atherosclerosis of different arterial sites. The limitations of miRNA profiling for such clinical application are also discussed.
摘要:
动脉粥样硬化疾病是世界范围内发病率和死亡率的主要原因。动脉粥样硬化可存在于不同的动脉区域中,并且作为单区域或多区域疾病。动脉粥样硬化的不同表型仅部分归因于获得性心血管危险因素和遗传孟德尔遗传。miRNA,在转录后水平调节基因表达,也可能导致这种异质性。许多miRNA通过调节内皮功能参与动脉粥样硬化的病理生理,平滑的血管细胞功能,血管炎症,血管中的胆固醇稳态,在其他生物过程中。此外,miRNAs在外周血中具有较高的稳定性,有可能作为非侵入性生物标志物用于动脉粥样硬化的诊断。然而,循环miRNA谱可能根据涉及的动脉区域而变化,考虑到动脉粥样硬化的表达,包括相关的分子表型,根据受影响的动脉区域而变化。在这次审查中,我们讨论了与不同动脉区域的动脉粥样硬化相关的特定循环miRNA谱,稳定动脉粥样硬化的常见循环miRNA谱,与涉及的动脉区域无关,和多区域动脉粥样硬化的循环miRNA特征。miRNA可以由用于区分不同动脉部位的动脉粥样硬化的简单非侵入性方法组成。还讨论了这种临床应用的miRNA谱分析的局限性。