Activation of HIF Protein may Become New Treatment for Ischemic Pathologies

A team of researchers from the Cardiovascular Research Center in Paria and CIC bioGUNE, an international center for biomedical research discovered that the activation of a cellular protein may be the key to a new treatment for ischemic pathologies.

The researchers used “an ischemic model provoked in a mouse leg through ligation of the femoral artery,” which stopped blood flow to the limb. Afterwards, the researchers artificially stimulated the production of HIF, a protein that cells use to respond to a lack of oxygen that is caused by poor blood flow. This artificial activation showed that “the mouse’s leg revascularised and no longer entered into a degenerative process.” The ability to artificially activate production of HIF can “stimulate revascularisation and the repair of the damaged organ following ischemia caused by the obstruction of a blood vessel preventing normal blood flow,” according to the researchers.

This high level of HIF production was achieved, according to the researchers, because “HIF is a protein which, when not required, degrades constitutively and this degradation is regulated by enzymes called PHDs.” The researchers state that after this process occurs, the enzymes hydroxylate HIF. As a result of that hydroxylation, the protein is then degraded.

“Therefore, when these enzymes are inhibited, HIF cannot degrade and so accumulates,” the researchers continued. “To inhibit PHDs, they use siRNAs.”

Ischemia caused by the obstruction of a blood vessel that prevents regular blood flow can result from a number of medical issues, the researchers explain, including thrombosis in a limb, myocardial infarction, or stroke. Because ischemia can occur from a number of original medical problems, the ability to use artificially-activated HIF may lead to a number of new treatments for several different conditions, the researchers concluded.