New research: Atherosclerosis shows similarities to tumour development
A new study from SDU and OUH shows that cells in atherosclerotic blood vessels grow in a way that resembles tumour development. The discovery provides new biological insights and may pave the way for treatment strategies.
Researchers from the University of Southern Denmark and Odense University Hospital have studied tissue from patients with atherosclerosis. They found that many of the cells in the diseased tissue carried the same genetic alteration and appeared to originate from a single ancestral cell that had divided repeatedly – a pattern otherwise associated with tumour biology.
In several patients, a large proportion of the cells were derived from one single mutated cell that had undergone many rounds of cell division.
– It’s striking how many cells in the tissue share the exact same genetic change. In several samples, more than 10 per cent of the cells – hundreds of thousands cells – carried the same alteration. It’s difficult to interpret this as anything other than all these cells originating from a shared ancestral cell that, at some point during disease development, acquired the mutation, says Lasse Bach Steffensen, Associate Professor at the Department of Molecular Medicine at the University of Southern Denmark.
What is atherosclerosis?
Atherosclerosis is a disease characterised by the accumulation of lipids, inflammatory cells and connective tissue within the walls of blood vessels. This buildup causes the vessels to become stiff and narrow, limiting blood flow.
The disease is initiated when cholesterol particles are retained in the vessel wall. The immune system perceives this as an injury, triggering a chronic inflammatory response. Over time, this leads to the formation of a mass of tissue and cells called a plaque, which can grow and progressively reduce blood flow through the vessel. Plaques can also rupture, causing the rapid formation of a thrombus, which can result in serious events such as heart attacks or strokes.
Atherosclerosis is influenced by both lifestyle and genetic factors. Smoking, high blood pressure, elevated cholesterol, obesity and physical inactivity all increase the risk. Although symptoms typically appear later in life, the disease process often begins during adolescence.
Atherosclerosis is a leading cause of heart attacks and strokes – and remains one of the most common causes of death in Denmark.
In a tumour, the disease often begins when a single cell acquires a genetic alteration that causes it to divide more than it should. As the daughter cells inherit the same alteration and continue to divide, a progressively larger mass of cells forms – what we call a tumour.
This finding offers a new perspective on atherosclerosis – a disease primarily associated with cholesterol, inflammation and lifestyle factors.
Although the researchers cannot yet determine whether the genetic alterations directly affect the disease, the mutations do not appear to occur randomly. Many of the affected genes could potentially influence cell behaviour and therefore the course of the disease.
A familiar disease with an unfamiliar aspect
Atherosclerosis is one of the leading causes of death in Denmark and worldwide. It causes thrombus formation in the heart and brain and is currently treated mainly with cholesterol- and blood pressure-lowering medication. There is still no treatment that directly targets the diseased vessel wall.
The results of the new study suggest that the cells in the affected tissue undergo numerous rounds of cell division – possibly due to mutations in their genetic material – similar to what is observed in tumour development.
– We’re not saying that atherosclerosis is a “blood vessel tumour”. But our data point to a possible interplay between genetic alterations and extensive cell division – something we typically associate with tumour biology, says Lasse Bach Steffensen.
What are genetic alterations?
Genetic alterations – also known as mutations – occur when changes arise in the DNA of cells. These changes happen naturally over the course of life and do not necessarily cause disease.
Most genetic alterations have no effect, but some can cause cells to behave differently – for example, by dividing more rapidly or acting abnormally.
In this study, the researchers found many cells in atherosclerosis-affected blood vessels that shared the same genetic alteration.
– This gives us a new biological understanding – and possibly new ideas for treatment.
Research made possible by patients
The study is based on tissue samples from patients who underwent vascular surgery at Odense University Hospital and Kolding Hospital. The samples were analysed using DNA sequencing and compared with the patients’ blood DNA to identify alterations unique to the vessel wall.
The tissue samples originate from a research biobank that has existed at OUH since 2009. The project is the result of many years of collaboration between surgeons, theatre nurses, biochemists and – most importantly – patients who voluntarily donated tissue for research.
Looking ahead
Lasse Bach Steffensen emphasises that the study so far includes only a small number of patients and that more research and other laboratory methods are needed to determine the significance of the genetic alterations in disease progression.
– We are now analysing tissue from many more patients to explore links between the mutation burden in atherosclerosis, disease stage, and clinical data. It’s possible we’ll begin to see atherosclerosis in a new light in the future, he says.
The study is published in JCI Insight and can be found here
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Meet the researcher
Lasse Bach Steffensen is an Associate Professor in the Cardiovascular & Renal Research unit, Department of Molecular Medicine.