(Press-News.org) Heart failure occurs when the heart cannot pump enough blood to meet the body's needs. It's a very common condition, affecting about six million people in the United States, but current therapies are not adequately effective at improving health and preventing deaths. A study published by Cell Press August 1st in the journal Cell reveals the key role of a family of molecules known as bromodomain and extraterminal domain (BET) proteins in activating genes that contribute to heart failure. The study also demonstrates that a BET-inhibiting drug can protect against heart failure in mice, opening up promising new avenues for the treatment of this devastating condition.
"New insights into the biology of heart failure are desperately needed to prompt new types of targeted therapeutic agents," says senior study author James Bradner of the Dana-Farber Cancer Institute and Harvard Medical School. "Our findings comprise significant progress toward fulfilling this clinical need, which is great news for heart failure patients."
Heart failure is a debilitating condition that causes fatigue, shortness of breath, organ damage, and early death. It is triggered by the activation of a large set of genes that cause the walls of the heart to thicken and develop scar tissue, impairing the organ's ability to pump blood normally. BET proteins can have a huge impact on gene activity because they belong to a class of molecules called epigenetic readers, which recognize special marks on DNA-protein complexes and attract gene-activating proteins to those spots. Bradner and his collaborators recently developed a potent BET inhibitor called JQ1, which shows promise as a potential anticancer therapy. But until now, nothing was known about the role of BET proteins in heart function.
To address this question, Bradner teamed up with study senior author Saptarsi Haldar of Case Western Reserve University School of Medicine and University Hospitals Case Medical Center. They found that BET proteins regulate the growth of heart muscle cells and activate a broad set of genes involved in heart failure. Treatment with JQ1 inhibited this abnormal pattern of gene activity and protected against heart-wall thickening, the formation of scar tissue, and pump failure in a mouse model of cardiac disease.
"Based on our findings, we are highly motivated to bring a drug-like derivative of JQ1 forward as a new type of heart failure drug for humans," Haldar says. "These compounds will shortly enter the clinic for therapeutic development in cancer, and we expect they can also be immediately developed into therapies for heart failure."
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Cell, Anand et al.: "BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure."
Promising compound could offer new treatment for heart failure
2013-08-01
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