Caring for patients with heart failure costs the United States $40 billion a year. Despite the condition’s enormous impact, few new treatments have been developed, and those that exist produce varied responses among patients. One major challenge to the development of new treatments has been the lack of genes that can be confidently associated with heart failure. Now, a study from researchers at Stanford University have identified a gene that appears to reduce the risk of heart failure and improve treatment outcomes, highlighting a possible target for the development of new drugs. The team state, that to their knowledge, this is the first time that heart function in relation to this gene has been studied. The study is published in Journal of the American College of Cardiology.
Previous studies show that individual patients with heart failure often respond differently to the same types of medical interventions. Some patients with heart failure who get medical therapy respond really nicely, with rteir heart function improving dramatically with medications. Whereas other patients, despite medical therapy, continue to worsen and require transplant. Therefore, the team wondered if there were genetic reasons for the discrepancies in treatment outcomes observed in the study, hypothesizing that a genetic variation might point toward a link.
The current study genotyped 866 heart-failure patients at the extremes of responses, those who had the best and worst responses to therapy. Results highlighted a gene near the region coding for the orexin receptor protein, which is known to be involved in the control of sleep, appetite and blood pressure. The group investigated further through a series of experiments, with data findings showing that the gene likely regulates how much of the receptor is made in a cell.
The lab then looked for evidence that the orexin receptor could be involved in heart function and found that its expression was increased in diseased human heart tissue. The researchers wondered whether this could mean that the receptor and its binding partner, orexin, have a protective function in the heart. Using a mouse model that mimics heart failure through artificially elevated levels of adrenaline, the researchers examined the role of the receptor and orexin. Results show that when orexin was given to the mice with failing hearts, those mice showed better systolic heart function than the mice that did not receive orexin.
Data findings show that hearts of mice missing the orexin receptor had greater diastolic heart dysfunction, relating to the relaxation phase of a heartbeat, another hint suggesting that the receptor is important for healthy hearts. The group explain that the finding has raised the question of whether insomnia medications that work by blocking the function of the orexin receptor could harm the heart, although this has not yet been studied.
The team state that the new study marks the first time the gene and receptor have been associated with heart failure and are eager to do further studies to explore this link. For the future, the researchers state they are hopeful that exploring the role of this receptor in the heart could inform new research, possibly leading to the development of novel therapies.
Source: Stanford University School of Medicine
