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Researchers from the National Center for Cardiovascular Research (CNIC) have discovered that neutrophils, a type of immune cell, behave differently in the blood during inflammatory processes and that one of these behaviors is associated with the presence of cardiovascular diseases.
The information provided by this study, which is published in the journal Nature, may allow, according to the researchers, the development of new treatments to minimize the sequelae caused by myocardial infarctions.
Neutrophils are a double-edged sword. These types of immune cells constitute the the organism’s main line of defense, but they are also capable of causing damage to healthy cells and the cardiovascular system. “Numerous studies have associated the presence of neutrophils in the blood with a greater severity and risk of suffering from cardiovascular problems,” says Georgiana Crainiciuc, first author of the study led by Dr. Andrés Hidalgo.
Although the simple thing would be to think of remove these neutrophils to protect the cardiovascular system, it is not possible, since, as the researcher points out, “it would generate a defenseless state against any pathogen that would be counterproductive for the body.
The authors decided to search and identify what specific types of neutrophils were responsible for vascular damage. To do this, they analyzed the behavior of cells using high-resolution intravital microscopy, a type of technology that allows cells to be visualized within blood capillaries in living animals.
The team designed a highly novel computational system capable of analyzing how cells behave in vessels by simple measurements of changes in the size, shape and movement of cells. In this way, they discovered that these immune cells show three patterns of behavior during the course of inflammatory processes, but that only one of them, characterized by a greater size and proximity to vessel walls, was associated with cardiovascular damage.
Through massive genetic analysis in animal models, the authors used the computational system to identify the molecules responsible for these harmful behaviors of neutrophils. This work showed that a single molecule, called Fgr, was responsible for the pathological behavior. This key information allowed us to select a drug that is highly effective in preventing inflammation and cell death after myocardial infarction. “The idea now is to continue with the necessary trials so that, in the future, this treatment can be used in patients,” explains Crainiciuc.
The researchers consider that their findings not only represent a great step when it comes to treating cardiovascular diseases, but also a milestone due to the methodology developed for the study of immune cells. “Current techniques are capable of analyzing a large number of genes and molecules per cell, which has made it possible to discover the existence of numerous cell populations related to the development of diseases”, indicates Dr. Miguel Palomino-Segura, co-first author of the study. However, he adds, “our model is unique because it allows identify cells, not because of its possible genetic profile, but by your type of activity during illness’.
«A key aspect is that neutrophils are capable of changing their form, activity and migratory capacity in a matter of seconds. This rapid metamorphosis can only be captured under the microscope, “adds Dr. Hidalgo.
To extract the full potential of these images, the researchers have collaborated with engineers from the Carlos III University of Madrid, who have developed new artificial vision techniques for measurements in living tissues.
The work, in which researchers from the Vithas Foundation, the University of Castilla la Mancha, the Singapore Science and Technology Agency (ASTAR) and the Universities of Harvard and Baylor (USA), among other centers, have also participated, has required intense computational development capable of systematically combine and compare large amounts of data coming from thousands of cells. “It is a technology that has been applied to other types of data, but this is the first example with in vivo microscopy data and the result has been surprising”, highlights Jon Sicilia, co-author and bioinformatician responsible for the analytical part of the draft.
With this new methodology, the authors hope that other scientific fields will benefit from their work. «The idea now is apply it to other scenarios such as infections or tumors, in which immune cells also play a crucial role in the development of the disease, “says Dr. Palomino-Segura.
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