Scientists on the Spot: Re-defining atherosclerosis through biobanks

Dr Monika M. Gladka from Amsterdam University Medical Center (The Netherlands), interviews Prof. Gerard Pasterkamp, Professor of Experimental Cardiology Department at the University Medical Center Utrecht in Utrecht (The Netherlands). Highlight: In this Onlife interview, Professor Pasterkamp talks about current challenges in the atherosclerotic field and the best ways to translate basic science into clinical practice. Professor Pasterkamp emphasizes that atherosclerosis is a complex multifocal arterial disease involving various genetic and environmental factors. To carefully study the characteristics of atherosclerotic plaques, the use of tissue biobanks is essential. The Athero Express biobank has existed for over 20 years and has contributed to several findings published over the years. One critical observation is that plaque characteristics have changed over the years due to changes in lifestyle and medication. Considering the extreme complexity of the disease, Prof. Pasterkamp explains that a single factor does not influence the development and progression of atherosclerosis but rather a combination of features, including genetic factors and age, sex, and lifestyle in general. Therefore, for diagnosis and risk stratification of atherosclerotic disease, many aspects need to be acknowledged. With having access to such an extensive number of human samples, the obvious challenges are the financial ones. Advanced analysis like proteomics, SNPs (Single nucleotide polymorphisms) analysis, or single-cell sequencing of plaques is costly—but in return, provides much valuable information. From a scientific perspective, state-of-the-art techniques have improved the basic knowledge about the disease, and the information described in textbooks 40 years ago no longer reflects the true characteristics of existing plaques. They apply to maybe 50% of them, says Prof. Pasterkamp. Hence, re-writing the textbooks and making a new definition of the vulnerable plaque is a necessary future aim. Lastly, he stressed that the direct translation of basic science to clinical practice needs some consideration. Different models to study atherosclerosis like cell-lines or mice are incredibly relevant to understanding disease mechanisms, but we need to realize that they might give different outcomes in humans. It would be essential to combine models and find a common aspect relevant to the disease. Additionally, for better translation of our findings to the clinic, it would be necessary to obtain lesions or vascular specimens of the early stages of the disease, which is, of course, a challenge. The molecular and genetic signature of early or moderate lesions would be important for diagnostic purposes and risk stratification. Conflict of interest: none declared. Biography: Dr. Monika Gladka is currently an Assistant Professor at University Medical Center in Amsterdam. Her current research focuses on understanding the molecular mechanisms that regulate cardiac repair, intending to identify new players to develop novel, improved gene therapies. She uses several state-of-the-art techniques such as single-cell sequencing, enabling an in-depth mechanistic understanding of the biological processes in injured cardiomyocytes. In 2016 and 2020, she received two prestigious Dr. E. Dekker personal grants from the Dutch Heart Foundation for heart repair research. She is actively involved in several cardiac societies acting as a board member of Young@Heart from the Netherlands Heart Institute and a nucleus member of the Scientists of Tomorrow from the European Society of Cardiology. Biography: Gerard Pasterkamp is a Professor in the Experimental Cardiology Department and the Laboratory of Clinical Chemistry at the University Medical Center Utrecht in The Netherlands. His research interests focus on cardiovascular biology and innovation in biomarkers and drug targets to diagnose and treat atherosclerotic disease. The research group houses the largest atherosclerotic plaque biobank worldwide, Athero Express—including more than 4500 patients. Professor Pasterkamp coordinates national and EU-based consortia to unravel biomarkers and mechanisms of atherosclerotic disease.