Oxidative Stress Signature in Coronary Artery Disease

According to the World Health Organization (WHO), cardiovascular disease (CVD), including, in particular, myocardial infarction and stroke, remains the most common cause of death worldwide. In light of current scientific reports, a growing body of evidence indicates a significant role of oxidative stress in the pathogenesis of these conditions. Oxidative stress is a consequence of excessive production of free radicals, whose direct measurement is considerably hindered due to their very short half-life. As a result, they do not accumulate in the blood at concentrations allowing direct detection using standard laboratory equipment. However, there are established methods for indirect assessment of the intensity of oxidative stress, which we plan to use within the project “Oxidative stress signature in coronary artery disease”.

Prof. Dr hab. Miłosz Jaguszewski, photo: Łukasz Bera For the purposes of the project, we selected a population of individuals who participated in the Moltest Bis screening programme in 2016–2017, based on low-dose computed tomography (LDCT) for early detection of lung cancer. Although the programme was not originally aimed at assessing cardiovascular disease, analysis of CT images enabled simultaneous assessment of the heart and coronary arteries. This allowed identification of patients with features of coronary artery disease (CAD), which is the main cause of myocardial infarction. Because individuals from the general population were recruited into the study, the analysed group included both healthy participants and patients with diagnosed CAD. This made it possible to divide the study population into two comparative groups and to analyse differences in oxidative stress parameters between them. The objective of these analyses is to identify potential circulating blood biomarkers whose altered concentrations may be causally associated with the development of coronary artery disease.

An important component of the project is the use of data collected nearly ten years ago, allowing long-term follow-up of study participants, including the occurrence of cardiovascular events such as myocardial infarction or stroke, as well as mortality. This approach enables prospective analyses of exceptional value for assessing cardiovascular risk, predicting life expectancy, and estimating the number of years lived in good health. Additionally, oxidative stress parameters will be compared between individuals who experienced disease-related events and those who remained free from vascular disease throughout the observation period.

The project also encompasses a broad range of molecular investigations. Blood samples were collected from all Moltest Bis participants and, following appropriate preparation, will undergo multidirectional laboratory analyses. This will allow assessment of which molecules present in the blood at the time of sampling may have influenced cardiovascular function and determined the risk of disease events and survival in subsequent years. Particular attention will be devoted to the analysis of genetic material (DNA), enabling the identification of genetic factors predisposing individuals to myocardial infarction or stroke. In the long term, these findings may support personalised cardiovascular risk assessment based on a patient’s genetic profile.

Prof. Dr hab. Miłosz Jaguszewski, photo: Łukasz Bera Another key element of the research will involve the analysis of microRNA — molecules that play a crucial role in regulating gene expression and constitute an important epigenetic mechanism. The aim of this component is to identify microRNAs potentially useful in the early diagnosis of asymptomatic patients at high risk of developing atherosclerosis.

Furthermore, extended molecular analyses are planned, including a detailed evaluation of the lipid profile. These studies will enable differentiation between lipid fractions with atherogenic potential and those that do not exhibit pathogenic properties, with particular emphasis on lipids subjected to oxidative processes. Since oxidative stress promotes oxidative modification of many biological compounds, we will investigate whether physiologically beneficial molecules may acquire pro-inflammatory and other properties influencing the progression of atherosclerosis once oxidised. The findings may contribute to improving lipid diagnostics in clinical practice.

The project is distinguished both by a carefully selected, well-characterised study population and by a wide range of advanced molecular analyses. Such a comprehensive approach will enable an in-depth understanding of the mechanisms underlying CAD and identification of key factors responsible for its development. Given that CVD remains the leading cause of death worldwide and that oxidative stress plays a significant role in its pathogenesis, this project should be regarded as being of fundamental scientific and clinical importance.