Researchers from the UC San Diego and the University of Iowa have identified a key piece in the complex molecular puzzle underlying heart failure, a serious and sometimes life-threatening disorder affecting more than 5 million Americans. In an opensource study published in Cell Reports, the team explores the heart’s progression from initial weakening to heart failure, and found that a protein, known as RBFox2, plays a critical role in this process.
Contrary to its name, heart failure does not mean the heart completely stops working, but rather that the heart muscle becomes weakened to the point that it can no longer pump enough blood for the body’s needs. Coronary artery disease, high blood pressure and heart defects are among various factors that can lead to heart failure, which has no cure and is currently treated with medications, lifestyle changes, oxygen and cardiac devices. In some cases, a heart transplant is required.
In the current study the researchers investigated the cellular changes that occur during the weakened heart muscle’s transition from working harder to maintain proper blood flow, known as the compensatory stage, to failing to sustain adequate blood supplies, known as decompensation. The team state that numerous signaling molecules have been shown to be part of the compensatory program, but relatively little was known about the transition to decompensation that leads to heart failure.
To answer this question, the team explored RBFox2, a gene splicing protein known to be involved in the heart’s early development and ongoing function. The lab wanted to know how RBFox2 might contribute to decompensation, given its vital role in heart functions. In their studies, the researchers restricted blood flow in mice to induce a condition similar to heart failure and then tested their RBFox2 protein levels over a period of weeks. Strikingly, they observed that RBfox2 protein was largely diminished in the hearts of live mice five weeks after the procedure.
The team also tested the reduction of the RBFox2 protein in mice specially-engineered to lack the protein. In these experiments, the mice lacking the RBFox 2 protein developed heart failure symptoms similar to those in the blood-restricted mice, suggesting a functional connection between the reduction of RBFox2 and decline of the heart muscle.
The researchers then sought to determine why, from a mechanistic point of view, the loss of RBFox2 would weaken the heart. To study this, they examined RBFox2-controlled changes in gene expression, which refers to the biological actions taken by genes, during various scenarios of heart development in mice. Specifically, the scientists compared changes detected in the hearts of RBFox2-deleted or blood-restricted mice to those that occur during post-natal heart ‘remodeling.
Remodeling is the process of heart strengthening that begins at birth and continues throughout childhood. The RBFox2 deletion-induced epigenetic changes are similar to those that occurred during blood restriction-induced heart failure, but opposite to those taking place during heart remodeling. The team state that this indicates that the normal developmental program for strengthening heart performance is reversed during heart failure.
The researchers learned that the RBFox2 protein is very important in keeping the heart muscle strong. The team summise that the research shows its diminished expression coincides with the weakening of the heart muscle. This strongly suggests a causal role for this protein in heart failure, adding that by understanding these mechanisms, the medical community may be able to find a way to prevent the decreased expression of RBFox2, which may help in preventing heart failure.
Source: UC San Diego
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.
Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.