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The short and long of noncoding sequences in the control of vascular cell phenotypes

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Abstract

The two principal cell types of importance for normal vessel wall physiology are smooth muscle cells and endothelial cells. Much progress has been made over the past 20 years in the discovery and function of transcription factors that coordinate proper differentiation of these cells and the maintenance of vascular homeostasis. More recently, the converging fields of bioinformatics, genomics, and next generation sequencing have accelerated discoveries in a number of classes of noncoding sequences, including transcription factor binding sites (TFBS), microRNA genes, and long noncoding RNA genes, each of which mediates vascular cell differentiation through a variety of mechanisms. Alterations in the nucleotide sequence of key TFBS or deviations in transcription of noncoding RNA genes likely have adverse effects on normal vascular cell phenotype and function. Here, the subject of noncoding sequences that influence smooth muscle cell or endothelial cell phenotype will be summarized as will future directions to further advance our understanding of the increasingly complex molecular circuitry governing normal vascular cell differentiation and how such information might be harnessed to combat vascular diseases.

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Abbreviations

CRISPR:

Clustered regularly interspaced short palindromic repeats

EC:

Endothelial cell

ENCODE:

Encyclopedia of DNA Elements

ETS:

E26 transformation specific

LncRNA:

Long noncoding RNA

LSS:

Laminar shear stress

Mir:

MicroRNA

MYOCD:

Myocardin

NAT:

Natural antisense transcript

NICD:

Notch intracellular domain

RACE:

Rapid amplification of cDNA ends

SMC:

Smooth muscle cell

SNP:

Single nucleotide polymorphism

SRF:

Serum response factor

TFBS:

Transcription factor binding site

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Acknowledgments

Work in the Miano lab is supported by National Institutes of Health grants HL-117907 and HL-112793. Work in the Long lab is supported by National Institutes of Health grant HL-112686 and a Scientist Development Grant from the American Heart Association (3670036). The authors apologize to those authors whose important work was not cited due to space constraints.

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  1. Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    Joseph M. Miano

  2. Center for Cardiovascular Sciences, Albany Medical College, Albany, NY, 12208, USA

    Xiaochun Long

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  1. Joseph M. Miano
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Correspondence to Joseph M. Miano.

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Miano, J.M., Long, X. The short and long of noncoding sequences in the control of vascular cell phenotypes. Cell. Mol. Life Sci. 72, 3457–3488 (2015). https://doi.org/10.1007/s00018-015-1936-9

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  • DOI: https://doi.org/10.1007/s00018-015-1936-9

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