Nature Medicine

Injury to blood vessels during angioplasty, a vessel clearing procedure, can lead to proliferation of vessel cells and renewed blockage. This complication occurs in almost a third of patients, who often must undergo repeat angioplasties. Now, a report in the January 21 online edition of Nature Medicine suggests that a simple one-hour treatment of carbon monoxide can cut down on the long-term damage to vessels after angioplasty—at least in rats.

The researchers found that low levels of carbon monoxide limited the proliferation of the smooth muscle cells that form the vessel walls. What's more, long-term administration of carbon monoxide in rats reduced the arteriosclerotic lesions caused by transplantation—a problem that occurs in people as a result of organ rejection after vessel grafting. It's already known that a carbon-monoxide-producing enzyme in the body protects against vessel injury from transplantation—but whether carbon monoxide could exert such effects directly has been unclear.

The technique needs to be tested next in pigs, whose circulatory systems more closely resemble that of people. But if these results continue to hold, they may represent an inexpensive and safe way to treat a range of vascular diseases and to boost the effectiveness of angioplasty.

Nature Medicine

Di'George's syndrome affects roughly 1 in 4,000 newborns, who can suffer from heart, thyroid, and other birth defects. One mystery surrounding the disorder has been the great variability of symptoms among afflicted individuals. Now, Peter Carmeliet in Leuven, Belgium and colleagues begin to answer why some individuals are only slightly affected by the disorder while for others the consequences are severely life-threatening, involving severe cardiac and vascular abnormalities.

It's been known for some time that the syndrome is associated with defects in chromosome 22. Large deletions in the chromosome, which remove approximately 3 million base pairs of DNA, take out a number of genes. These genes include a gene called Tbx1, implicated in mouse studies as a key gene in Di'George's syndrome. In the January 21 online edition of Nature Medicine, the investigators report that they have honed in on a separate gene that appears to affect the severity of this disorder. Mice lacking this gene, VEGF, had birth defects resembling those found in Di'George's patients. In addition, VEGF appeared to affect the amount of Tbx1 produced in mice.

The authors next took their experiments into zebrafish, a model of vertebrate development. In zebrafish with a deletion in chromosome 22, mutations in VEGF increased the severity of heart defects. What does all this mean for people? The definitive answer awaits further experiments. But the authors present initial evidence that mutations in VEGF are associated with an increased risk for cardiovascular birth defects in individuals with the characteristic deletion in chromosome 22.