From bench to emergency room bedside

How do you move from elegantly constructed mouse knockouts like the ones presented at the linkurl:Keystone Symposium on Molecular Mechanisms of Cardiac Disease and Regeneration;http://www.the-scientist.com/blog/display/23130/ here in Santa Fe, New Mexico, to pesky wild-type humans who often seem to court heart attacks? If you?re linkurl:Elizabeth Nabel,;http://www.genome.gov/17015041 director of the linkurl:National Heart, Lung, and Blood Institute,;http://www.nhlbi.nih.gov/new/press/05-01-26.htm the path is fairly direct. When she?s not figuring out how to keep most of the participants of this meeting in grants, Nabel still runs a lab. Her talk tonight started with a reminder that in the adult vasculature, there?s a close relationship between angiogenesis, proliferation of the smooth muscle that makes up the heart, and inflammation. Her lab?s search for molecular and cellular mechanisms that regulate the proliferative response led them to p27, a cyclin-dependent kinase inhibitor. p27-null mice display abnormal but generally benign hyperplasia of many organs. Following a wire injury to the femoral artery, however, the femoral lumen fills completely with vascular smooth muscle cells. That fits with the hypothesis that p27 regulates smooth muscle proliferation. But there?s an intense inflammation response that Nabel and colleagues didn?t expect. It turns out that when p27 is upregulated, it inhibits the proliferation of inflammatory cells that migrate into vascular lesions and the proliferation of local vascular smooth muscle cells; when it?s downregulated or absent, inflammation and hyperplasia rule the day. If that ? plus the molecular mechanisms, which the Nabel lab seems to have worked out ? were the whole story, it would be just another tantalizing thread in cardiac development and angiogenesis. But the p27 story has played out in drug-eluting stents, Nabel pointed out. Two of those drugs, sirolimus (rapamycin) and paclitaxel, cause changes that lead to upregulation of p27. That could explain how such coronary stents inhibit further atherosclerosis. For Nabel, however, the bench-to-bedside link became even more direct once her talk was over. Just as the next speaker, the University of Pennsylvania?s linkurl:Jonathan Epstein,;http://www.med.upenn.edu/camb/faculty/db/epstein.html was wrapping up, one unfortunate participant began having a seizure. Nabel was one of the first responders. I?d say having the director of an NIH institute ? whom, it perhaps goes without saying, trained as a physician ? make sure your airway, breathing, and circulation were OK while you waited for paramedics to arrive is a real rubber hitting the road kind of bench-to-bedside experience.

From bench to emergency room bedside

The Scientist ARCHIVES

Become a Member of

Meet the Author

Ivan Oransky

Related Research Resources

Study Confirms Safety of Genetically Modified T Cells

Research Resources

Podcasts

Webinars

Videos

Infographics

eBooks

TaqMan Probe & Assays: Unveil What's Possible Together

Meet Aunty and Tackle Protein Stability Questions in Research and Development

Detecting Residual Cell Line-Derived DNA with Droplet Digital PCR

Making Real-Time PCR More Straightforward

Products

Product News

Biotium Launches New Phalloidin Conjugates with Extended F-actin Staining Stability for Greater Imaging Flexibility

Latest AI software simplifies image analysis and speeds up insights for scientists

BioSkryb Genomics and Tecan introduce a single-cell multiomics workflow for sequencing-ready libraries in under ten hours

Agilent BioTek Cytation C10 Confocal Imaging Reader