Balancing Act

Blood vessels in a mouse retina. Endothelial cells are blue, perivascular cells are red and green.

The key to blood vessel growth is balance: too much, or not enough, of any one signaling molecule can have disastrous consequences.  Embryos can fail to develop.  Vessels can burst, clog, and leak.  Vessels can also respond a little too vigorously to a tissue’s plea for more resources, growing in a messy disarray of dead-end tubes that blood can’t flow through.

While papers on blood vessels date back more than 150 years, we continue to have new insights into their biology.  We learned about the cells that make up the vessels: endothelial cells, which form the actual tube itself, and perivascular cells, which sit just next to the endothelial cells.  Capitalizing on this, we started growing “vessels” in dishes, which lets us study how blood vessels respond to signals in their environment.  We discovered small, secreted molecules in living things that encourage new blood vessel growth.  We developed ways to inhibit those signals.  And still, there is more to learn.

The field of blood vessel growth (angiogenesis) spans many disciplines.  Beyond understanding the basics as they relate to developmental biology, blood vessels reach into cancer, eye disease, stroke, heart disease, gastrointestinal disease, complications of pregnancy, and more.  The benefit of this is that discoveries in one field can inform the others.  Across these fields, there have been increasing reports of blood vessel regulation by microRNAs.

MicroRNAs are tiny strands of RNA that regulate protein expression by degrading messenger RNA (which contains the “message” from DNA) before the message gets translated to protein.  Thousands of microRNAs have been discovered, but not all have been ascribed a function, and many have functions beyond those initially reported. They are named with numbers, generally in the order of their discovery.

A paper published by Dauren Biyashev and colleagues in the journal Blood on March 15th 2012 describes a new role for microRNA 27b.  In the complex web of arrows that can be drawn to “explain” the dizzying number of factors that prompt blood vessel growth or stasis, microRNA 27b may sit near the top, regulating both vessel sprouting and artery/vein assignment, by acting on several distinct pathways.

Biyashev and colleagues found that microRNA 27b levels respond to pro- and anti-angiogenic signals in the environment, and that this one microRNA can prevent the translation of at least six different proteins that regulate blood vessel formation.  As such, it is a dial that can be tuned with broad-reaching downstream consequences.

As a master regulator, MicroRNA 27b helps keep many signals “just right” during blood vessel development.  Understanding the central role of this microRNA, and the growth factors that regulate it, may provide new rationale for existing anti-angiogenic drugs, or lead to the development of new drugs that target the microRNA itself.

__________________________

miR-27b controls venous specification and tip cell fate, Blood, March 15 2012, Vol 119 (11).

Angiogenesis is controlled by miR-27b associated with tip cells, Blood, March 15 2012, Vol 119(11).

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