Santulli Gaetano
Columbia University Medical Center, New York, NY, USA.
Adv Exp Med Biol. 2015;887:53-77. doi: 10.1007/978-3-319-22380-3_4.
Endothelial cells (EC) and vascular smooth muscle cells (VSMC) are the main cell types within the vasculature. We describe here how microRNAs (miRs)--noncoding RNAs that can regulate gene expression via translational repression and/or post-transcriptional degradation--distinctively modulate EC and VSMC function in physiology and disease. In particular, the specific roles of miR-126 and miR-143/145, master regulators of EC and VSMC function, respectively, are deeply explored. We also describe the mechanistic role of miRs in the regulation of the pathophysiology of key cardiovascular processes including angiogenesis, atherosclerosis, and in-stent restenosis post-angioplasty. Drawbacks of currently available therapeutic options are discussed, pointing at the challenges and potential clinical opportunities provided by miR-based treatments.
内皮细胞(EC)和血管平滑肌细胞(VSMC)是脉管系统中的主要细胞类型。我们在此描述微小RNA(miR)——可通过翻译抑制和/或转录后降解来调节基因表达的非编码RNA——如何在生理和疾病状态下独特地调节EC和VSMC的功能。特别是,分别深入探讨了EC和VSMC功能的主要调节因子miR-126和miR-143/145的具体作用。我们还描述了miR在调节关键心血管过程(包括血管生成、动脉粥样硬化和血管成形术后支架内再狭窄)的病理生理学中的机制作用。讨论了当前可用治疗方案的缺点,指出了基于miR的治疗所带来的挑战和潜在临床机遇。