Protein Clusters in Heart Muscle Similar to Amyloid Plaques in Brain Tissue
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Reviewed By Louise Chang, MD
Heart failure involves a harmful buildup of a protein called desmin, says Giulio Agnetti, PhD, a postdoctoral research fellow at Johns Hopkins University School of Medicine and the University of Bologna, Italy.
"Just like pistons have to be in the right place for a car engine to work, desmins have to be in the right place or the heart will not contract," he tells WebMD.
The changes led to the formation of debris-like protein clusters in heart muscle, similar to the amyloid plaques seen in the brain tissue of Alzheimer's patients, he says.
The protein alterations, which were reversed by surgically repairing the heart, occurred at the onset of heart failure. Since then, the researchers found the same chemical modifications to desmin in the heart muscle in four people diagnosed with heart failure.
The research was reported at the American Heart Association Scientific Sessions 2009, in Orlando, Fla.
Research Ties Desmin to Weakening Heart
Misshaped desmin proteins and amyloid-like debris had been previously reported in 2005 in mice genetically altered to develop chronic heart failure, providing the first biological link between the two chronic diseases.
Studies since have also reported desmin changes in failing animal hearts, but none detailed what the chemical changes were or how they might affect organ function.
The new research, Agnetti explains, is believed to be the first to tie common underlying structural changes in desmin to malformations observed in the heart as it weakens, strains to pump blood, and starts to fail. Their results are also believed to be the first to suggest that toxic, desmin-like amyloids could form in response to stress placed on the heart.
In the latest experiment, the researchers analyzed proteins in heart tissue samples collected from a group of dogs whose hearts had been surgically altered to beat irregularly, become stressed, and fail -- that is, mimic heart failure. Additional tissue samples were analyzed from another group of healthy dogs.
The researchers found accumulating amyloid-like debris containing desmin in the damaged heart tissue but not in the normal tissue.
"In our preliminary research, we found that desmin changed chemically and structurally and turned into a toxic species," Agnetti says.
Moreover, the debris-like clusters are similar to the amyloid plaques seen in the brain tissue of Alzheimer's patients, he says.
"Our study leads us to believe that desmin plays a key role in heart failure," he says. "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."
American Heart Association spokesman Ralph Sacco, MD, of the University of Miami, tells WebMD that the research raises the prospect of treating the root cause of heart failure by preventing the formation of desmin amyloid.
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Giulio Agnetti, PhD, postdoctoral research fellow, Johns Hopkins University School of Medicine; University of Bologna, Italy.
Ralph Sacco, MD, University of Miami.
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