German team maps 1st-ever proteome of the human heart

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 - heart geometry

The first-ever proteome of the healthy human heart is complete, a team at the Technical University of Munich has reported—thanks to the successful logging of nearly 11,000 proteins and billions of cells.

Sophia Doll and colleagues at the German Heart Centre published their findings this week in Nature Communications, where they called their discovery “an atlas of the heart.” The team measured 16 anatomical regions of the heart and three major cardiac cell types, according to the study, through the use of high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, Doll et al. tallied more than 10,700 individual proteins in the tissue. Help from researchers at the Max Planck Institute of Biochemistry in Planegg, Germany, ensured quick analysis, reaching an eventual ability to measure a whole heart in less than two days.

While profiling the heart’s valves, cardiac chambers and blood vessels, Doll and co-authors wrote they broke down heart cells into three categories: cardiac fibroblasts, smooth muscle cells and endothelial cells.

“Looking at the protein atlas of the human heart, you can see that all healthy hearts work in a very similar manner,” Doll said in a release from TUM. “We measured similar protein compositions in all the regions with few differences between them. We were also surprised to find that the right and left halves of the heart are similar, despite having quite different functions.”

Doll and her colleagues wrote they constructed the proteome with the goal of better identifying differences between healthy and diseased hearts, since previous studies have used diseased heart tissue for mapping or limited their research to select cell types.

“This approach has two problems,” Doll said. “First, the results did not give a full picture of the heart across all its regions and tissues; and second, comparative data on healthy hearts were often missing. Our study has eliminated both problems. Now the data can be used as a reference for future studies."

Doll and co-authors proved this through comparison of their heart atlas with cardiac proteomes of patients suffering from atrial fibrillation. They found the tissue differed the most in diseased hearts when it came to proteins responsible for supplying energy to heart cells; these proteins, which are responsible for energy metabolism, were compromised in all diseased hearts.

However, the researchers wrote, the changes in proteins also differed between patients, emphasizing the need for personalized care in cardiovascular practice.

“These findings show us how important personalized medicine is,” Markus Krane, deputy director of the Department of Cardiovascular Surgery at TUM, said in the release. “Although all the patients had very similar symptoms, we see from the data that a different molecular dysfunction was responsible in each case. We need to learn to recognize and treat such individual differences—especially in cardiac medicine.”