MicroRNA therapeutics in cardiovascular medicine

Abstract

Cardiovascular diseases are the most common causes of human morbidity and mortality despite significant therapeutic improvements by surgical, interventional and pharmacological approaches in the last decade. MicroRNAs (miRNAs) are important and powerful mediators in a wide range of diseases and thus emerged as interesting new drug targets. An array of animal and even human miRNA-based therapeutic studies has been performed, which validate miRNAs as being successfully targetable to treat a wide range of diseases. Here, the current knowledge about miRNAs therapeutics in cardiovascular diseases on their way to clinical use are reviewed and discussed.

Histone Deacetylase 9 Promotes Angiogenesis by Targeting the Antiangiogenic MicroRNA-17–92 Cluster in Endothelial Cells

“…Mature miRs are generated by 2 major RNase III endonucleases, namely Dicer and Drosha. 16,17 Inhibition of Dicer or Drosha expression impaired endothelial cell sprouting and neovascularization, 18,19 and several proangiogenic and antiangiogenic miRs have meanwhile been identified, among them the miR-17-92 cluster. 20 The miR-17-92 cluster is a polycistronic miR cluster encoding for miR-17, miR-18a, miR-19a/b, miR-20a, and miR-92a, which are transcribed as one common primary miR precursor.…”

Regulatory Noncoding RNAs in Cardiovascular Disease: Shedding Light on ‘Dark Matter’

“…5 Acting as genetic switches or fine-tuners, miRNAs are key regulators of diverse biological and pathological processes including growth, development, organogenesis, apoptosis, cell proliferation and differentiation, myocardial infarcts (MI), ischemia/reperfusion (I/R) injury and heart failure (HF), providing glimpses of undiscovered regulatory mechanisms and potential therapeutic targets for the treatment of CVD. [6][7] The present mini review focuses primarily on recent updates on the basic miRNA biology, CVD-miRNA based research progress and functional significance of circulating noncoding RNAs. We also discuss their potential use as biomarkers and/or therapeutic targets in heart disease.…”

“…Let-7c expression alterations were strikingly similar in failing human and fetal hearts. 7 A recent report suggests that elevated expression of cardiac-related miRNAs (miR-208a, miR-133, miR-133a, miR-133b, miR-145, miR-499, miR-499-5p and miR-1) in a manner similar to that of cardiac troponin iso-enzymes. [33][34][35] The use of some of these miRNAs, particularly miR-208a as a biomarker for MI remains controversial.…”

Engineered microRNA therapeutics

“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24] A number of distinct human disease states could be treated with engineered microRNA therapeutics including multiple liver diseases where hepatocyte function has been dysregulated, 3,19,22 cardiac ischemia and other related complications in the heart, 11,13,16 fibrosis in multiple tissue types, 17,18,25 inflammatory disease states such as rheumatoid arthritis and other inflammatory conditions with macrophage involvement, 15 and in various cancers. 14,20,23,26 For the sake of brevity, miR-122 and miR-21 will be used as examples of validated microRNA targets.…”