Researchers identify speed of gene transcription as a new therapeutic target for vascular disease

by Anne Grimm, Leipzig University

edited by Sadie Harley, reviewed by Andrew Zinin

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Atherosclerosis develops when deposits known as plaques build up in the walls of blood vessels over many years. These plaques are particularly dangerous when they become unstable and rupture: Blood clots can form, blocking blood vessels and potentially causing a heart attack or stroke.

A research team at Leipzig University's Faculty of Medicine has discovered a previously unknown mechanism that contributes to plaque instability: the speed at which vascular cells transcribe their genetic information into RNA. By selectively blocking this process, the researchers were able to reduce both pathological changes in the cells and typical features of unstable plaques.

The findings have been published in the journal Signal Transduction and Targeted Therapy.

The study focuses on endothelial cells, which line the inside of blood vessels and form a functional barrier between the blood and the vessel wall. In atherosclerosis, these cells are continuously exposed to inflammatory stimuli and altered patterns of blood flow. This can cause them to lose their original identity and instead acquire pathological characteristics, leading to progressive loss of function and increased permeability. Cells that have undergone this transformation are particularly common in unstable atherosclerotic plaques.

The researchers at the University of Leipzig Medical Center investigated how quickly endothelial cells alter their gene expression during this transition. Their attention focused on a protein complex known as the super elongation complex (SEC), which controls a crucial step in fast gene transcription. For many genes, the transcription process normally pauses shortly after it begins. The SEC protein complex can release this pause, enabling genes to be activated very rapidly.

The study shows that this is precisely the process activated at the onset of the cells' pathological transformation. This finding was also confirmed in tissue from patients with atherosclerosis: Levels of components of the SEC protein complex were particularly high in endothelial cells that were already showing signs of this transition.

"We were able to show that when endothelial cells undergo pathological changes, it is not only which genes are activated that matters, but also how quickly this cellular transcription takes place. This early phase of gene regulation offers a largely unexplored therapeutic target that is currently also gaining relevance in cancer therapy," says study leader Professor Jes-Niels Boeckel, professor of experimental cardiology at Leipzig University and head of a research group at the Department of Cardiology at the University of Leipzig Medical Center.

Targeted slowing of vascular cell transformation

In human endothelial cells, the researchers inhibited the SEC protein complex using experimental compounds. This slowed the pathological transformation of the cells, allowing the vascular cells to retain the functional properties required to maintain the vascular barrier.

In the reverse experiment, increased activity of a key component of the SEC complex caused endothelial cells to develop disease-related characteristics even in the absence of additional stimuli.

The effect was also evident in a more physiologically relevant model: In cardiac organoids—three-dimensional models of heart tissue grown in the laboratory—inhibiting the SEC reduced both excessive collagen deposition and impaired heart muscle cell function.

Of particular relevance for potential future therapeutic use were the studies conducted in an atherosclerosis model. Treated mice showed a lower plaque burden, reduced macrophage infiltration and fewer pathological endothelial cells. SEC inhibition reduced the extent of vascular changes both preventively and therapeutically in mice with established atherosclerosis.

The importance of the mechanism was further confirmed by analyzing 1,048 sections of human plaques from the AtheroExpress biobank at Utrecht University in the Netherlands.

"What is particularly exciting is that we were able to trace this mechanism from human vascular samples and molecular analyses through to functional models. Inhibiting RNA elongation not only reduced changes in individual cells, but also had a beneficial effect on characteristics of atherosclerotic plaques," says Boeckel.

The inhibitors used in the study are still experimental. However, compounds that slow gene transcription by targeting CDK9, a component of the complex, are already undergoing clinical trials in cancer medicine. Further studies will investigate whether this approach can be applied to vascular diseases. The first steps toward a new therapy for unstable plaques have now been taken.

More information

Karoline E. Kokot et al, Targeting super elongation complex-driven RNA polymerase II elongation reduces plaque vulnerability, Signal Transduction and Targeted Therapy (2026). DOI: 10.1038/s41392-026-02962-4

Key medical concepts

Endothelial CellsAtherosclerosis

Clinical categories

Cardiology Provided by Leipzig University Who's behind this story?

Sadie Harley

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Citation: Researchers identify speed of gene transcription as a new therapeutic target for vascular disease (2026, September 29) retrieved 29 September 2026 from https://medicalxpress.com/news/2026-09-gene-transcription-therapeutic-vascular-disease.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.