Using high-resolution mass spectrometry-based proteomics, researchers have created a spatial and cell-type-resolved atlas of the human heart. They hope their cardiac proteome will make it easier to identify differences between healthy and diseased hearts. The heart map is available at maxqb.biochem.mpg.de.
Details of the research were recently published in Nature Communications by a team from the Max Planck Institute of Biochemistry (MPIB) and the German Heart Centre at the Technical University of Munich (TUM).
Not only did the team determine the protein profile of cells in all the regions of the heart, such as heart valves, cardiac chambers and major blood vessels, they also investigated the protein composition in three different cell types: cardiac fibroblasts, smooth muscle cells, and endothelial cells. In this way, they were able to map the distribution of proteins in the various regions of the heart.
Previous studies focused mostly on individual cell types, or they used tissue from diseased hearts, which is problematic, according to Sophia Doll of the MPIB and lead author of the study, "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."
"Looking at the protein atlas of the human heart, you can see that all healthy hearts work in a very similar manner. We measured similar protein compositions in all the regions with few differences between them," adds Doll. "We were also surprised to find that the right and left halves of the heart are similar, despite having quite different functions: the right half pumps oxygen-poor blood to the lungs, while the left half pumps oxygen-rich blood from the lungs to the body."
To illustrate the usefulness of the heart proteomic map, the team applied it to define molecular changes in patients suffering from atrial fibrillation. They compared their values with the cardiac proteomes of patients with AFib and learned more about the cause of the disease. The tissue of the diseased hearts was most different in proteins responsible for supplying energy to the cells. In addition, although the proteins involved in energy metabolism were changed in all the patients, those changes differed between individuals.
The team credits technological advances with making this research possible. They used high-sensitivity sample preparation, peptide fractionation, and an advanced label-free LC–MS workflow to quantify more than 11,000 proteins, substantially more than previous studies.
Image: Front: Drawing of a cardiac muscle, background: excerpt from a heatmap, an overview of the proteins analyzed for the proteomic map. Image courtesy of Doll, Kraue, Menzfield/MPIB