Increasing the number of blood vessels that supply the heart muscle has been considered a therapeutic approach in patients with heart failure. Despite the theoretical benefit of such an approach being clear, clinical studies so far haven’t shown much success. Now, researchers from the Sanford Burnham Prebys Medical Discovery Institute have found a master regulator involved in this process, offering a new angle to treat heart failure.
Mark Mercola headed up the research with his group at the Sanford Burnham Prebys Medical Discovery Institute (SBP); they published their findings in the journal Nature Communications last week.
Angiogenesis is a process where new blood vessels are formed, and this is essential for developing organs, as well as injured organs, in supplying blood delivering energy to fuel the cells. In heart failure (HF), part of the heart muscle may have become starved of blood and consequently oxygen, ultimately turning into scar tissue over time.
A way to fix this would be to increase angiogenesis in a patient suffering from HF, restoring or at least improving heart function after injury.
The researchers in this study have found a protein which may just be the answer. “We found that a protein called RBPJ serves as the master controller of genes that regulate blood vessel growth in the adult heart,” said Mercola. “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.”
It works as a molecular “brake” as it stops a number of pro-angiogenic and associated genes from being expressed in the contractile heart cells themselves—the cardiomyocytes. In a mouse model, they genetically removed the Rbpj gene (in cardiomyocytes only) and observed increased microvascularization of the mouse’s heart.
Importantly, in contrast to other studies targeting angiogenesis in mice, this finding occurred without cardiac structural defects, or worsening heart function, even at a later age.
The authors suspect that previous studies have failed since they’ve targeted single factors rather than a master regulator of angiogenesis.
“We used mice that lack RBPJ to show that it plays a novel role in myocardial blood vessel formation (angiogenesis)--it acts as a master controller, repressing the genes needed to create new vessels,” said Diaz-Trelles, lead author of the study. “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.”
Coupled with being a druggable target, the SBP researchers are also looking at the therapeutic applications for diseases other than heart failure. “Inhibitors of RBPJ might also be used to treat peripheral artery disease, and activators might be beneficial in cancer by inhibiting tumor angiogenesis,” Diaz-Trelles added.
- here’s the Nature Communications abstract