Study reveals factors behind blood vessel cells' fate
EU-funded researchers have identified a mechanism that controls the fate of cells that make up blood vessel walls. The findings could lead to the development of new drugs to promote blood vessel repair and treat diseases of the blood vessels.
The study, published in the Journal of Clinical Investigation, was supported in part by the MYORES (Multi-organismic approach to study normal and aberrant muscle development, function and repair) project, which is funded under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6).
Blood vessel walls contain muscle cells called vascular smooth muscle cells (VSMCs). These cells are able to alter the diameter of the blood vessel by contracting and relaxing. In this way, they can control blood pressure and direct blood to areas of the body that need it most, for example. However, under certain conditions, VSMCs switch from this 'contractile' mode to a 'synthetic' mode, during which the cells divide and produce large amounts of proteins to form a tissue matrix.
The ability of these cells to switch between these two modes is thought to have evolved in order to aid in the creation of new blood vessels and to facilitate wound healing. However, the switch to the synthetic mode has also been implicated in a number of diseases involving the blood vessels, including high blood pressure and atherosclerosis.
Yet despite the importance of the switch in these diseases, the mechanisms behind it remain poorly understood. In this latest study, German researchers discovered that two small RNA (ribonucleic acid) molecules (microRNAs or miRNAs) known as miR-143 and miR-145 play a key role in triggering and maintaining the contractile mode in mice.
MicroRNAs are tiny stretches of RNA that regulate the production of proteins. The researchers found that mice lacking miR-143 and miR-145 had extremely low numbers of contractile VSMCs and higher-than-usual numbers of tissue matrix-producing VSMCs in their large arterial blood vessels.
Further investigations revealed that the two microRNAs are needed to trigger the contractile mode and to maintain healthy blood pressure in mice. Mice lacking the microRNAs also turned out to have signs of blood vessel disease, leading the authors to suggest that their findings could bring about new drug development.
In an accompanying article, Michael Parmacek of the University of Pennsylvania in the US describes the study as 'exciting' and points out that it raises as many questions as it answers. For example, what regulates the production and activity of the microRNAs in the VSMCs, how do they control blood pressure, and are they involved in conditions such as atherosclerosis?
"The answers to these questions promise to provide new insights into our understanding of cardiovascular development and the pathogenesis of vascular proliferative syndromes," he writes.
Dr Parmacek concludes: "These VSMC-restricted microRNAs, which target unique combinations of SMC genes, provide an efficient mechanism to fine-tune cardiovascular homeostasis and the response of the vessel wall to injury. This important discovery will open the door to new avenues of investigation and potentially future therapies for vascular diseases."
The MYORES Network of Excellence brings together 37 research groups in 24 institutions in 7 European countries. It started in 2005 and is scheduled to come to a close at the end of 2009. The aim of MYORES is to study the molecular and genetic factors governing muscle development, function and repair.
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