Helping heart cells regenerate
Researchers at the University of Texas (UT) Southwestern Medical Center have discovered a protein that works in tandem with others to slow cell division in the heart. This discovery has the potential to reverse a developmental block and help heart cells regenerate, offering a path toward treating a variety of conditions in which heart muscle is damaged. Current pharmaceutical approaches attempt to halt the cycle of heart muscle loss, even as strain further leads to further damage, causing more cells to die. That’s according to UT Southwestern physician-researcher Hesham Sadek, a professor of internal medicine molecular biology and biophysics. Indeed, no treatment exists to rebuild heart muscle. To that end, in 2013, Sadek’s team determined that the protein Meis1 plays an important role in stopping heart cell division. Although deleting this gene in mice extends the window of heart cell division, it is transient, and heart cells missing this gene eventually slow and stop their multiplication. The team then came upon Hoxb13. They genetically engineered mice in which the gene that codes for Hoxb13 was deleted, and the animals behaved much like those in which just the gene for Meis1 was deleted. The result: the window for heart cell rapid division was increased but still closed within a few weeks. When the researchers shut off Hoxb13 in adult mouse hearts, their cell division had a brief resurgence, enough to prevent progressive deterioration after an induced heart attack but not enough to promote significant recovery. Their findings appeared April 22, 2020, in Nature.
Heart failure hormone has role in sepsis
Scientists at Temple University School of Medicine have identified a role for the hormone B-type natriuretic peptide (BNP) in sepsis. BNP is produced by the heart and lowers blood pressure, and it is a prognostic biomarker in heart failure. It also has been proposed as a biomarker in sepsis, where blood pressure can become dangerously low in serious cases. However, whether BNP participated in lowering blood pressure in sepsis had not been clear. The authors showed that the c-Jun N-terminal kinase signaling, which also leads to harmful changes in mitochondrial metabolism during sepsis, activated BNP production and led to hypotension. The authors concluded that the present study provides mechanistic insight into the factors underlying septic shock and proposes the design of two treatment strategies to manage critically ill patients with hypodynamic sepsis. They reported their results in the April 23, 2020, issue of JCI Insight.
Speeding up ER treatment
A research team has unveiled a new protocol using blood tests to determine whether a patient is having a heart attack, thereby reducing wait times and overcrowding in emergency departments. That’s according to a new study from the University of Texas (UT) Southwestern Medical Center that was published April 22, 2020, in JAMA Open. “Patients are more reluctant to come to the ER [emergency room] with heart-related symptoms during the COVID-19 outbreak. We do not want those with medical emergencies to avoid the hospital due to concern for risk from the virus,” explained cardiologist Rebecca Vigen, assistant professor of internal medicine at UT Southwestern. Vigen and her team found that a new protocol for using high-sensitivity cardiac troponin testing can improve efficiency in the ER by quickly identifying those who are not having a heart attack. Troponins are released upon damage to the heart muscle. The protocol incorporates the HEART score – history, electrocardiogram, age, risk factors, and troponin.
Cheating cell death improves infarct outcomes
Researchers at Henan University and Temple University have demonstrated that blocking the interaction of (TNF)-related apoptosis-inducing ligand (TRAIL) with its receptor, the death receptor 5 (DR5), prevented cell death and reduced tissue damage after an induced heart attack via both direct and indirect mechanisms. The authors tested the effects of TRAIL blockade in rats, pigs and monkeys. They found that blocking the interaction between TRAIL and its receptor reduced cell death, but it also prevented the migration of immune cells and subsequent inflammation at the site of injury. “Our findings indicate that TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic strategy” for treating heart attacks, the authors wrote. Their work appeared in the April 22, 2020, issue of Science Translational Medicine.