A protein studied as a potential treatment for cardiovascular disease could actually trigger heart failure, according to a study released today by the Sanford-Burnham Medical Research Institute in La Jolla and the Stanford University School of Medicine.
According to Sanford-Burnham, researchers have long sought ways to activate the APJ protein, which sits on the surface of cells in many of the body's organs and senses changes to its external environment, as a way to treat heart disease.
The latest research, published in today's edition of the journal Nature, found that APJ has a second function, reacting to internal mechanical changes within the organ.
An enlarged heart, for example, could lead APJ to respond in a way that sets a course toward heart failure, according to the study.
A team led by Pilar Ruiz-Lozano, formerly assistant professor at Sanford-Burnham and now associate professor of pediatrics at Stanford, tested enlarged hearts in mice that didn't have the APJ protein, and the organs kept functioning because they could not sense the danger.
"In other words, without APJ, ignorance is bliss -- the heart doesn't sense the danger and so it doesn't activate the hypertrophic pathways that lead to heart failure,'' Ruiz-Lozano said. "This tells us that, depending on how it's done, activating APJ might make matters worse for heart disease patients.''
The benign function for APJ comes when it binds with a hormone called apelin. Previous studies showed that the combination of APJ and apelin directs beneficial processes such as embryonic heart development, maintenance of normal blood pressure, and new blood vessel formation.
Apelin is not involved in the harmful actions by APJ, which responds simply to changes within the organ, according to the research.
