Thesis Reveals How Atherosclerosis Develops Differently in Men and Women

A doctoral thesis defended in the Faculty of Medicine at the University of Tartu fundamentally changes the current understanding of atherosclerosis treatment. The results show that at the cellular level, this chronic disease progresses differently in men and women, laying the groundwork for more precise and individualized therapies.

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Atherosclerosis is a chronic disease in which fatty and calcified deposits accumulate on the walls of arteries, narrowing them. Over time, these plaques can completely block the vessel and lead to a heart attack or a stroke.

Because the condition is driven by widespread health problems in modern society, such as high blood pressure and diabetes, cardiovascular diseases associated with atherosclerosis have become one of the leading causes of death worldwide. Approximately 19,8 million people die due to atherosclerosis each year.

The catastrophic impact of the disease motivated the author of the thesis, Katyayani Sukhavasi, to investigate its molecular nature in greater depth.

“Existing genetic studies identify risk factors and loci as isolated signals,” she explained. “But to study this disease, we need to uncover the complex interactions between genes and their environment, which act in networks.”

In her doctoral thesis, Sukhavasi thus combined single-cell RNA sequencing and gene regulatory network analysis to identify the molecular mechanisms that influence the course of atherosclerosis. This integrated approach enabled her, for the first time, to define the cellular regulatory pathways that drive the progression of the disease.

The study shows that although the cellular structure of vascular plaques is similar in men and women, the processes occurring within these cells differ. In women, the disease tends to progress through the calcification of arterial cells, which stiffens the vessels – making them resemble bone tissue – and accelerates their deterioration. In men, atherosclerosis is more often accompanied by inflammation, which makes plaques more prone to rupture, resulting in a higher risk of heart attack.

“Biological sex is not merely a risk factor but a fundamental variable that dictates the molecular course of atherosclerosis,” emphasized Sukhavasi. “Instead of relying on a one-size-fits-all approach, we can now move toward targeted therapies. For women, this could mean developing drugs that prevent the bone-like transformation observed in arterial cells. For men, the focus might shift to stabilizing plaques and reducing harmful inflammation.”

Katyayani Sukhavasi defended her doctoral thesis, titled “Single-cell RNA sequencing analysis integrated with human gene-regulatory networks provides mechanistic insights of advanced atherosclerosis in men and women”, in early November. Her supervisors were Associate Professor Arno Ruusalepp from Tartu University and Associate Professor Johan L. M. Björkegren from Sweden’s Karolinska Institute. The work was also awarded the 2025 Research Award of the Estonian Society of Cardiology.