Catalucci Daniele, Latronico Michael V G, Condorelli Gianluigi
Department of Medicine, Division of Cardiology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0613, USA.
Ann N Y Acad Sci. 2008 Mar;1123:20-9. doi: 10.1196/annals.1420.004.
Growing evidence indicates that microRNAs (miRNAs) are involved in a variety of basic biological processes, including cell proliferation, apoptosis, stress response, hematopoesis, and oncogenesis. In fact, bioinformatic analysis predicts that each miRNA may regulate hundreds of targets, suggesting that miRNAs may play roles in almost every biological pathway. Information from recent studies indicate that miRNAs are involved in the regulation of cardiac development and pathophysiology. Notably, knockout of miRNA-1 was associated with cardiac defects, including regulation of cardiac morphogenesis, electrical conduction, and cell cycle control. Our group has identified a critical role of miRNA-1 and miRNA-133 in determining cardiac hypertrophy and has shown an inverse correlation of expression with cardiac hypertrophy, in vitro, in murine models and in human disease states associated with cardiac hypertrophy. Remarkably, in vivo experiments with a single infusion of antagomir-133 oligonucleotide, a small cholesterol-conjugated RNA sequence suppressing endogenous miRNA, induced marked and sustained cardiac hypertrophy. Shedding light on the role of this new class of RNA molecules in heart physiology and pathology may reveal possible future therapeutic applications for the treatment of heart diseases.
越来越多的证据表明，微小RNA（miRNA）参与多种基本生物学过程，包括细胞增殖、凋亡、应激反应、造血作用和肿瘤发生。事实上，生物信息学分析预测每个miRNA可能调控数百个靶标，这表明miRNA可能在几乎所有生物学途径中发挥作用。近期研究信息表明，miRNA参与心脏发育和病理生理学的调控。值得注意的是，miRNA-1基因敲除与心脏缺陷有关，包括心脏形态发生、电传导和细胞周期调控。我们的研究小组已确定miRNA-1和miRNA-133在决定心肌肥大中起关键作用，并在体外、小鼠模型以及与心肌肥大相关的人类疾病状态中显示出其表达与心肌肥大呈负相关。值得注意的是，在体内实验中，单次输注抗miR-133寡核苷酸（一种抑制内源性miRNA的小的胆固醇缀合RNA序列）可诱导明显且持续的心肌肥大。阐明这类新的RNA分子在心脏生理学和病理学中的作用，可能会揭示未来治疗心脏病的潜在治疗应用。
