In a groundbreaking study that challenges long-held perceptions of atherosclerosis, researchers from the University of Southern Denmark and Odense University Hospital have unveiled a startling genetic dimension to this prevalent cardiovascular disease. Traditionally known as a condition driven by cholesterol accumulation, inflammation, and lifestyle factors, atherosclerosis is now being examined through the lens of genetic mutations and clonal cell expansion—phenomena previously associated predominantly with cancer biology.
The team meticulously analyzed human vascular tissue samples obtained from patients undergoing vascular surgeries. By employing advanced DNA sequencing technologies, they identified that a significant fraction of cells within the diseased arterial walls carried identical genetic alterations, tracing back to a common ancestral cell. This discovery points to a clonal proliferation within plaques, analogous to the rapid cellular divisions seen during tumorigenesis. Surprisingly, in some patients, more than ten percent of the arterial cells shared these mutations, amounting to hundreds of thousands of clonally expanded cells.
This revelation not only redefines the biological underpinnings of atherosclerosis but also suggests that cellular mutation and proliferation mechanisms may play an integral role in plaque development. Unlike cancer, however, the researchers emphasize that atherosclerosis should not be classified as a “blood vessel tumor.” The genetic mutations, though reminiscent of those driving malignancies, may act more subtly in influencing the behavior and progression of diseased vascular cells.
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Historically, atherosclerosis has been characterized by the build-up of lipids and immune cells within arterial walls, leading to plaque formation and subsequent vessel narrowing. These plaques, which evolve through a complex interplay of cholesterol deposition and chronic inflammation, often culminate in life-threatening events such as heart attacks and strokes. Current clinical interventions primarily focus on managing cholesterol levels and blood pressure but do not directly target the diseased vessel tissue at the cellular or genetic level.
By identifying large clonal populations in plaque tissue, this study shines a light on a previously unappreciated layer of complexity within atherosclerosis. The presence of mutated cell clones suggests a potential mechanism by which plaques might expand or stabilize differently, influenced by the genetic “blueprint” carried by proliferating cells. The study’s lead researcher, Associate Professor Lasse Bach Steffensen, underlines that these findings open new pathways for research that could transform therapeutic strategies.
One of the study’s critical technical advancements was the comparison of mutated DNA from plaque cells with the patients’ blood DNA, enabling the identification of alterations specific to the diseased vessel wall. This approach minimized confounding factors and provided clear evidence of localized genetic changes potentially driving disease progression. The comprehensive sequencing data revealed mutations clustered in genes that plausibly impact cellular behavior, including proliferation, survival, and response to environmental stressors.
The implications of this clonal expansion are profound. If these mutated cell populations contribute actively to plaque growth or instability, understanding their genetic drivers could herald novel treatments aimed at halting or reversing disease progression. Such therapies might target pathways involved in cell division or mutation repair, areas currently explored extensively in oncology yet relatively unexplored in cardiovascular medicine.
Despite these exciting advancements, the researchers are cautious in their interpretation. The study, involving a limited patient cohort, requires validation in larger populations and experimental models to delineate causality. Furthermore, whether these genetic alterations are causative in plaque formation or secondary consequences of chronic disease remains to be established. Nonetheless, the evidence unmistakably points to the significance of clonal cellular behavior in atherosclerosis, reframing it as a dynamic and genetically influenced disease process.
This discovery also underscores the invaluable role of patient-donated tissue samples collected over more than a decade at Odense University Hospital. The meticulous collection, preservation, and analysis of these human samples have provided unparalleled insights that extend beyond traditional epidemiological or biochemical approaches. The collaboration between surgeons, laboratory scientists, and patients forms a solid foundation for future translational research poised to impact clinical practice.
Looking forward, the research team plans to expand their investigation to include a broader patient base and integrate clinical data correlating mutation burden with disease severity and outcomes. Such longitudinal studies could reveal whether the extent of clonal expansion predicts cardiovascular events or responsiveness to therapy. Moreover, advances in single-cell sequencing and spatial transcriptomics may enable detailed mapping of mutated cell populations within plaques, illuminating their interactions within the vascular microenvironment.
Notably, this study challenges the biomedical community to reassess the binary distinction between cancerous and non-cancerous proliferative diseases. The concept that atherosclerosis involves cellular proliferation driven by genetic mutations opens up a conceptual bridge linking cardiovascular pathology with oncogenic processes. This could inspire innovative interdisciplinary research blending oncology, genetics, and cardiovascular science to uncover shared molecular mechanisms and therapeutic targets.
In summary, the identification of clonal cell populations bearing shared genetic alterations in atherosclerotic plaques invites a transformative perspective on one of the world’s leading causes of death. By integrating genetic insights with classical risk factor paradigms, science edges closer to unraveling the complex biology of vascular disease. The prospect of genetically informed diagnostics and treatments offers hope for improved patient outcomes, representing a crucial step toward personalized cardiovascular medicine.
Subject of Research: Human tissue samples
Article Title: Mutational landscape of atherosclerotic plaques reveals large clonal cell populations
News Publication Date: 8-Apr-2025
Web References:
https://insight.jci.org/articles/view/188281
http://dx.doi.org/10.1172/jci.insight.188281
Image Credits: Lasse Bach Steffensen, University of Southern Denmark
Keywords: Atherosclerosis, genetic alterations, clonal expansion, vascular disease, DNA sequencing, plaque biology, cardiovascular genetics, cell proliferation, mutation, tumor biology analogy, personalized medicine, cardiovascular pathology
Tags: advanced vascular tissue analysisatherosclerosis genetic mutationscancer biology in atherosclerosiscardiovascular disease researchclonal cell expansion in atherosclerosisDNA sequencing in vascular studiesinflammation and genetic factorsplaque development mechanismsrevolutionary findings in cardiovascular healthtumor development parallelsUniversity of Southern Denmark study
