(Vienna, 09 October 2023) A joint research group from the Medical University of Vienna and King's College London has presented a "proteome atlas" of atherosclerotic plaques that reveals important gender differences in the development and prognosis of atherosclerosis. The study identified four key proteins that are more predictive of future cardiovascular mortality than conventional methods. These findings, currently published in the journal Circulation Research, could inform the prevention and treatment of heart attack and stroke.
Heart attacks and strokes remain the leading causes of death in Europe and the USA. In a groundbreaking step towards improving the prevention and treatment of these dangerous diseases, the research groups led by Johann Wojta from the Department of Internal Medicine II at the Medical University of Vienna and Manuel Mayr from King's College London and Professor of the Cardiovascular Cluster at MedUni Vienna have conducted a pioneering study.
This study involved the largest proteomic analysis of atherosclerotic plaques (hardened areas in the arterial wall) to date. Using 219 surgically removed endarterectomy specimens from the carotid arteries of 120 patients, the researchers investigated specific patterns in the expression of proteins in atherosclerotic lesions. Key findings were replicated in an independent cohort from the Netherlands using plaques from an additional 200 patients.
Men have more inflammation, women more calcification
The results showed that inflammation and calcification, two interlinked pathophysiological processes in the development of atherosclerotic plaques, show sex-specific differences. Interestingly, inflammatory plaques were found more frequently in men, whereas calcified plaques were more common in women. However, the study showed that not only the inflammatory plaques in males but also the calcified plaques in women are prognostically relevant and associated with a high risk of cardiovascular events.
Analysis of the proteome can complement conventional histological examinations and imaging techniques in clinical practice. In the present study, a protein signature of four key proteins - calponin, protein C, serpin H1, and versican - was identified that proved superior to conventional methods such as histology or imaging in predicting future cardiovascular mortality. These four proteins were selected by machine learning algorithms and capture key pathophysiological processes in atherosclerosis.
"These findings not only contribute to our knowledge of gender differences in pathophysiological processes contributing to the development and progression of atherosclerosis, but also make an important contribution to the identification of patient-groups at increased risk for cardiovascular events in the future," explains co-study leader Johann Wojta.
According to the research team, the results of this study have the potential to fundamentally advance our understanding of gender differences in atherosclerosis at a molecular level, with potential relevance for the prevention and treatment of cardiovascular disease.
Publication: Circulation Research
Proteomic Atlas of Atherosclerosis: The Contribution of Proteoglycans to Sex Differences, Plaque Phenotypes, and Outcomes
Theofilatos K, Stojkovic S, Hasman M, van der Laan SW, Baig F, Barallobre-Barreiro J, Schmidt LE, Yin S, Yin X, Burnap S, Singh B, Popham J, Harkot O, Kampf S, Nackenhorst MC, Strassl A, Loewe C, Demyanets S, Neumayer C, Bilban M, Hengstenberg C, Huber K, Pasterkamp G, Wojta J, Mayr M. Proteomic Atlas of Atherosclerosis: The Contribution of Proteoglycans to Sex Differences, Plaque Phenotypes, and Outcomes. Circ Res. 2023 Sep 15;133(7):542-558. doi: 10.1161/CIRCRESAHA.123.322590. Epub 2023 Aug 30. PMID: 37646165; PMCID: PMC10498884.