Small, non-coding RNAs: their modifications, and their detection in cardiovascular diseases

Abstract

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide, with common mechanisms including endothelial dysfunction, vascular inflammation, and altered cellular signaling. Small non-coding RNAs (sncRNAs), such as microRNAs and tRNA-derived fragments (tRFs), have emerged as key regulators of cardiovascular homeostasis and pathology, influencing processes like cardiac remodeling, ischemia-induced vascular remodeling, and plaque formation. This thesis investigates the epitranscriptomic regulation of sncRNAs and their functional consequences in cardiovascular disease. It demonstrates that 5’ isomiRs, exemplified by ISO-miR-411, are differentially processed and exhibit distinct targetomes, affecting angiogenesis under ischemic conditions. The role of m6A-modified miRNAs, such as miR-494-3p, in intracranial atherosclerosis is also highlighted, revealing modulation of endothelial tight junction proteins and vascular integrity. Furthermore, tRFs were assessed as potential circulating biomarkers for acute stroke, showing promising but currently limited diagnostic performance due to technical challenges. Finally, a DNA-functionalized hydrogel platform was developed for rapid, sequence-specific detection of sncRNAs, demonstrating robust and homogeneous signal response. Collectively, this work integrates molecular insights with translational applications, providing new understanding of sncRNA regulation in CVD and advancing strategies for biomarker development and rapid diagnostics.