A team of scientists are believed to have found proof from studies in animals and humans supporting a link between Alzheimer’s disease and chronic heart failure. Apparently, these two are amongst the ten leading causes of death in the United States.
Scientists claimed that they have recognized three changes in the chemical make-up of a key structural protein called desmin in heart muscle cells in dogs. The changes could perhaps lead to the development of debris-like protein clusters similar to the amyloid plaques seen in the brain tissue of Alzheimer’s patients. These debris-like protein clusters are also called as amyloid-like oligomers containing desmin in heart muscle. Moreover, the protein alterations, which were reversed by surgically repairing the heart seems to have occurred at the onset of heart failure. Further experiments seem to have found the same chemical modifications to desmin in the heart muscle in four people already diagnosed with the disease.
Misshaped desmin proteins and amyloid-like debris apparently had been previously reported in 2005 in mice genetically altered to develop chronic heart failure. This in turn may have provided the first biological link between the two chronic diseases. Since then, studies have also noted to have reported desmin changes in failing animal hearts. However, none could be able to detail what the chemical changes were or how they may affect organ function.
This study is known to be the foremost one to tie common essential structural changes in desmin to malformations seen in the heart as it weakens, strains to pump blood and starts to fail. Their findings are also noted to be the first to suggest that toxic, desmin-like amyloids could form in reply to stress placed on the heart.
Lead author of the study and protein biochemist Giulio Agnetti, Ph.D. said that, “Our study leads us to believe that desmin plays a key role in heart failure. Now we have a chemical target to research further and help us investigate what could be the underlying biological cause of heart failure and if it is like Alzheimer’s, an amyloid-related disease.”
“Just as significantly, our study raises the prospect of testing new treatment options for heart failure by moving beyond treating symptoms of the disease and getting to the root of the matter, preventing these desmin amyloids from forming and impairing heart function from the start,” says Agnetti, a postdoctoral research fellow at both the Johns Hopkins University School of Medicine and its Heart and Vascular Institute, and the University of Bologna and its National Institute for Cardiovascular Research, in Italy.
Symptoms of heart failure may include fatigue, shortness of breath and enlargement of the heart. The latest study seems to have begun with an analysis of proteins included in heart tissue samples collected from a group of dogs whose hearts had been surgically altered to beat irregularly. More so, their hearts appear to have become stressed and fail. Additional tissue samples were taken from another group of healthy controls.
Subsequently, the authors were believed to have compared these samples in order to look for structural and chemical changes in desmin. Supposedly, these are found in all heart muscle cells and are a key component of the intermediate filaments that make up the scaffolding, or muscle cell support structure.
According to the team, the same muscle structure could possibly have become disorganized in heart failure. The team’s analysis may perhaps have yielded at least three chemical differences in each desmin protein in response to heart failure. Additional tests showed that phosphate molecules seem to have attached at two spots within the protein’s structure. They also appear to have found accumulating amyloid-like debris, containing desmin, inside the damaged heart tissue.
When they performed surgery restoring the dogs’ heart pumping function to normal, they found phosphorylated sites seem to have been typically reverted to normal. Evidently, the amlyoid-like oligomers also began to disappear. Moreover, tissue samples from nearly four people with heart failure were noted to have shown similar desmin modifications. It appears to be not surprising as these changes in the so-called ‘scaffolding’ structure of the heart could be able to produce toxic debris.
“But what is most interesting about our findings is that we have shown that these chemical changes and debris are related to impaired heart function, which, ultimately, may explain how and why the heart can fail,” says senior author of the study, Jennifer Van Eyk, Ph.D., a Johns Hopkins professor and director of Hopkins’ NHLBI Proteomics Group and the Proteomics Center at Johns Hopkins Bayview Medical Center, where the protein analysis took place.
Agnetti claimed that the team’s protein analysis was merely made possible in the last 15 years with the progress of technologies for detailed chemical analysis, such mass spectrometry and gel electrophoresis. Earlier, scientists were noted to have mostly focused on genetic changes and their relationship to disease, as opposed to disease-causing alterations to proteins that take place after proteins are made. Study authors next plan may be to analyze each of the desmin modifications in order to determine the subsequent biological impact of each chemical change.
The findings of the study have been presented at the American Heart Association’s (AHA) annual Scientific Sessions in Orlando.