What's being hailed as a medical breakthrough could lead to the development of new drugs that minimize the damage to the heart caused by heart attacks.

The discovery by a team from the Sanford Burnham Prebys Medical Discovery Institute (SBP) and Stanford University published in Nature Communications reveals a key control point in controlling the formation of new blood vessels in the heart. More important, it offers a novel approach to treat heart disease patients.

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Dr. Mark Mercola, Ph.D., professor in SBP's Development, Aging, and Regeneration Program, said what their research found was that a protein called RBPJ serves as the "master controller" of genes that regulate blood vessel growth in the adult heart.

"RBPJ acts as a brake on the formation of new blood vessels. Our findings suggest that drugs designed to block RBPJ may promote new blood supplies and improve heart attack outcomes," said Dr. Mercola.

In a heart attack, the ensuing loss of heart muscle affecting a large enough area can severely reduce the heart's pumping capacity. This causes labored breathing and makes day-to-day tasks difficult. This condition, called heart failure, arises within five years in at least one in four heart attack patients.

Heart muscle dies in a heart attack because it's starved of oxygen caused by blockage of an artery supplying the heart. If the heart muscle had an alternative blood supply, more muscle would remain intact, and heart function would be preserved.

This being the case, an obvious solution is to find ways to promote the formation of additional blood vessels in the heart.

Dr. Ramon Díaz-Trelles, Ph.D., staff scientist at SBP and lead author of the study, noted that studies in animals have shown that having more blood vessels in the heart reduces the damage caused by ischemic injuries, "but clinical trials of previous therapies haven't succeeded."

"The likely reason they have failed is that these studies have evaluated single growth factors, but in fact building blood vessels requires the coordinated activity of numerous factors. Our data show that RBPJ controls the production of these factors in response to the demand for oxygen," he said.

The team used mice that lack RBPJ to show that it plays a novel role in myocardial blood vessel formation (angiogenesis). RBPJ acts as a master controller, repressing the genes needed to create new vessels.

"What's remarkable is that removing RBPJ in the heart muscle did not cause adverse effects--the heart remained structurally and functionally normal in mice without it, even into old age."

"RBPJ is a promising therapeutic target. It's druggable and our findings suggest that blocking it could benefit patients with cardiovascular disease at risk of a heart attack. It may also be relevant to other diseases," said Dr. Pilar Ruiz-Lozano, Ph.D., associate professor of pediatrics at Stanford and adjunct professor at SBP, co-senior author.

She said inhibitors of RBPJ might also be used to treat peripheral artery disease, and activators might be beneficial in cancer by inhibiting tumor angiogenesis.

TagsRBPJ, Sanford Burnham Prebys Medical Discovery Institute, Stanford University, Dr. Mark Mercola, Dr. Ramon Díaz-Trelles, Dr. Pilar Ruiz-Lozano, heart attack, Heart