Captured by Mount Sinai Medical Center
Researchers at Mount Sinai School of Medicine have identified a new drug target that may treat and/or prevent heart failure. The team evaluated failing human and pig hearts and discovered that SUMO1, a so-called “chaperone” protein that regulates the activity of key transporter genes, was decreased in failing hearts. When the researchers injected SUMO1 into these hearts via gene therapy, cardiac function was significantly improved. This research indicates that SUMO1 may play a critical role in the pathogenesis of heart failure. The data are published online in Nature.
Led by Roger J. Hajjar, MD, Director of Mount Sinai’s Wiener Family Cardiovascular Research Laboratories, and the Arthur and Janet C. Ross Professor of Medicine, Mount Sinai School of Medicine, the team has been evaluating the transporter gene SERCA2a in patients with severe heart failure as part of the CUPID (Calcium Up-regulation by Percutaneous administration of gene therapy In cardiac Disease) trial. When delivered via an adeno-associated virus vector—an inactive virus that acts as a medication transporter—into cardiac cells, SERCA2a demonstrated improvement or stabilization with minimal side effects. However, they found that while injection with SERCA2a restored cardiac function, over time the new SERCA2a became dysfunctional. This indicated that something else upstream from SERCA2a was causing the dysfunction in the heart.
Changwon Kho, PhD and Ah Young Lee, PhD, two postdoctorate students in the study of cardiac proteins at Mount Sinai School of Medicine, identified SUMO1 as the regulator of SERCA2a, showing that it enhanced its function and improved its stability and enzyme activity. Dr. Hajjar and his team studied human and animal models and found that when SUMO1 was decreased, SERCA2a became dysfunctional, showing that SUMO1 plays a protective role. When the team injected SUMO1 as a gene therapy, they found that it protected SERCA2a from the oxidative stresses and dysfunction that are prevalent in heart failure.
“Our experiments over the last four years beginning with the discovery of SUMO1 as an interacting protein of SERCA2a have shown that it plays a critical role in the development of heart failure,” said Dr. Hajjar. “In fact, SUMO1 may be a therapeutic target at the earliest signs of development, and may be beneficial in preventing its progression, a much-needed advance for the millions suffering from this disease.” Read more…
Posted in P4 Medicine Update 10/5/11, Personalized, Personalized Health Care, Personalized Medicine, Preventive
Tagged cardiac function, cardiac proteins, cardiology, cardiovascular disease, CUPID, gene therapy, heart failure, Mount Sinai, oxidative stresses, P4 Medicine Update 10/5/11, prevent, SERCA2a, SUMO1, therapeutic target, transporter genes, treat
Captured by American Society of Nephrology (ASN)
Acute kidney injury (AKI) is a common – but preventable — complication after surgery that can lead to other complications or even death. The use and development of biomarkers will help physicians diagnose and treat acute kidney injury. Three protein measurements indicate who has a high risk of developing kidney injury after heart surgery, according to two studies appearing in an upcoming issue of the Journal of the American Society of Nephrology.
“To date, these are the largest studies in adults and children comparing and validating the performance of three of the most frequently studied markers of kidney injury,” said author Chirag Parikh, MD, PhD (Yale University School of Medicine).
The studies included more than 1,200 adults and 300 children undergoing heart surgery throughout North America. Frequent urine and blood samples were collected to measure levels of three proteins — urine interleukin-18 (IL-18) and urine and plasma (blood) neutrophil gelatinase-associated lipocalin (NGAL)—and assess their ability to predict who will develop kidney injury after surgery.
Traditionally, kidney trouble is assessed by measuring the blood protein creatinine, which is not ideal because it has a delayed result—it does not pick up early damage and injury to the kidneys.
“We demonstrated that the three proteins in our study identify kidney injury soon after surgery and 24 to 48 hours earlier than creatinine, and shows a similar result,” according to Parikh.
Risk of kidney injury was especially high—more than six times higher—for adults and children with the highest levels of urine IL-18. Plasma NGAL also predicted kidney injury in adults, whereas urine NGAL was not an accurate predictor in adults once results were adjusted for other factors. Urine IL-18 and urine, but not plasma, NGAL were accurate predictors in children.
Doctors may wish to measure these urine or blood proteins immediately after surgery to predict which patients are at high risk of developing kidney injury. These patients might benefit from kidney protective therapies. Read more…
Posted in P4 Medicine Update 8/16/11, Predictive, Preventive
Tagged acute kidney injury, American Society of Nephrology, biomarkers, blood protein, diagnose, heart surgery, kidney, kidney injury, kidney surgery, P4 Medicine Update 8/16/11, predict, predictor, preventable, protective therapies, protein, risk, surgery, therapies, treat