MicroRNAs in Angiogenesis and Vascular Smooth Muscle Cell Function

Abstract

The Human Genome Project was barely completed in 2003 before a new quest was launched: this time, in a search for short stretches of RNA called microRNA. The belief that these miniature molecules, which had only been discovered a decade earlier, were major regulators of genetic function gained momentum in the intervening years and sparked a worldwide interest in the physiologic and pathologic roles of microRNAs in the human body. These single-stranded, noncoding molecules of RNA, spanning to lengths of only 25 nucleotides, appear to modulate a range of cellular events by modifying the primary function of messenger RNA (mRNA): protein synthesis. The first regulatory RNA, lin-4, was discovered by Victor Ambros in 1993. Later, Andy Fire, Craig Mello, and David Baulcombe discovered small interfering RNA (siRNAs) and established the role of small noncoding mRNA in regulating cell function under a variety of conditions. The field has exploded in directions that no one could have predicted. We now know that small RNAs are expressed in most eukaryotic cells and regulate a remarkable number of cellular functions.1 The exact mechanism of action of microRNAs is unclear; however, it is believed that these molecules bind to select, noncoding regions of mRNA through traditional Watson and Crick base pairing, repressing or increasing expression of the genetic transcript and its corresponding protein. It is theorized that each molecule of microRNA regulates more than 100 distinct molecules of mRNA, with unknown but potentially far-reaching effects in the human body.2 Already multiple reports implicate an array of distinct microRNAs in cardiac and skeletal muscle myogenesis, apoptosis, regeneration, hypertrophy, fibrosis, and cardiac function. Investigators use microRNA expression profiling to identify specific microRNAs in a host of human and animal cells. Quantitative mass spectrometry measures protein levels in cells following the introduction of a specific microRNA …