The Stress-Biomarker Axis in Atherosclerosis Driven by Organelle, Oxidative and tRNA and miRNA Dynamics

Session

Pharmaceutical and Natural Sciences

Description

Cardiovascular diseases (CVD) remain the leading cause of death globally, causing approximately 19.8 million deaths in 2022, accounting for 32% of all deaths. Atherosclerosis (AS), one of the leading causes of these diseases, is a chronic inflammatory vascular disease closely associated with oxidative stress and endothelial dysfunction. Organelle stress, particularly endoplasmic reticulum (ER) and mitochondrial stress, exacerbates oxidative stress by leading to the overproduction of reactive oxygen species (ROS). In turn, oxidative stress impairs organelle function, creating a vicious cycle. This interaction accelerates atherosclerotic plaque formation, chronicizes inflammation in the vascular wall, and impairs plaque stability, increasing the risk of cardiovascular events. In recent years, it has been shown that transfer RNAs (tRNAs), which are involved in classical protein synthesis, not only mediate translation but also regulate gene expression via tRNA-derived small RNAs (tRFs, tRNA-derived fragments). Certain tRF subtypes have been implicated in endothelial dysfunction and the proliferation/migration processes of vascular smooth muscle cells (VSMCs). Increased tRNA degradation under cellular stress conditions (ER stress, hypoxia, oxidative stress) is directly related to the inflammatory microenvironment seen in atherosclerosis. In addition to miRNAs, circulating tRFs are promising new biomarker candidates for early diagnosis and monitoring disease progression. Our in silico analyses using publicly available GEO datasets (GSE28858 and GSE202937) revealed significant increases in the ER stress sensor protein IRE1 and the oxidative stress marker NRF2 in patient samples. Furthermore, significant differences were observed in the expression levels of specific tRNAs ( tRNA-Gly-1-7, TRNL2, TRNK, TRKTTT; 12.6- to 7.6-fold) and miRNAs (miR-468, miR-199a, miR-1248, miR-376c; 7.8- to 8.9fold). Our findings suggest that organelle and oxidative stress in the pathogenesis of atherosclerosis can be monitored not only at the cellular level but also through circulating RNA biomarkers, and that tRFs may be active regulators of the disease.

Keywords:

Atherosiclerosis, organel stress, oxidative stress, tRNA, miRNA, biomarker

Proceedings Editor

Edmond Hajrizi

ISBN

978-9951-982-41-2

Location

UBT Lipjan, Kosovo

Start Date

25-10-2025 9:00 AM

End Date

26-10-2025 6:00 PM

DOI

10.33107/ubt-ic.2025.353

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Oct 25th, 9:00 AM Oct 26th, 6:00 PM

The Stress-Biomarker Axis in Atherosclerosis Driven by Organelle, Oxidative and tRNA and miRNA Dynamics

UBT Lipjan, Kosovo

Cardiovascular diseases (CVD) remain the leading cause of death globally, causing approximately 19.8 million deaths in 2022, accounting for 32% of all deaths. Atherosclerosis (AS), one of the leading causes of these diseases, is a chronic inflammatory vascular disease closely associated with oxidative stress and endothelial dysfunction. Organelle stress, particularly endoplasmic reticulum (ER) and mitochondrial stress, exacerbates oxidative stress by leading to the overproduction of reactive oxygen species (ROS). In turn, oxidative stress impairs organelle function, creating a vicious cycle. This interaction accelerates atherosclerotic plaque formation, chronicizes inflammation in the vascular wall, and impairs plaque stability, increasing the risk of cardiovascular events. In recent years, it has been shown that transfer RNAs (tRNAs), which are involved in classical protein synthesis, not only mediate translation but also regulate gene expression via tRNA-derived small RNAs (tRFs, tRNA-derived fragments). Certain tRF subtypes have been implicated in endothelial dysfunction and the proliferation/migration processes of vascular smooth muscle cells (VSMCs). Increased tRNA degradation under cellular stress conditions (ER stress, hypoxia, oxidative stress) is directly related to the inflammatory microenvironment seen in atherosclerosis. In addition to miRNAs, circulating tRFs are promising new biomarker candidates for early diagnosis and monitoring disease progression. Our in silico analyses using publicly available GEO datasets (GSE28858 and GSE202937) revealed significant increases in the ER stress sensor protein IRE1 and the oxidative stress marker NRF2 in patient samples. Furthermore, significant differences were observed in the expression levels of specific tRNAs ( tRNA-Gly-1-7, TRNL2, TRNK, TRKTTT; 12.6- to 7.6-fold) and miRNAs (miR-468, miR-199a, miR-1248, miR-376c; 7.8- to 8.9fold). Our findings suggest that organelle and oxidative stress in the pathogenesis of atherosclerosis can be monitored not only at the cellular level but also through circulating RNA biomarkers, and that tRFs may be active regulators of the disease.