studY of M6a in Cardiac Arrest

Sudden cardiac arrest (SCA) is the third leading cause of death in Europe. Not only suffering cardiovascular issues, many SCA survivors are prone to considerable long-term neurological impairments due to a transient ischemic state of the brain inducing neuronal death. Neuropsychologists identified a wide range of neuropsychological deficits in these patients besides the well-known amnesic syndrome. Consequences of SCA can be devastating for both heart and brain, and underline the need for novel therapeutic approaches and biomarkers that can be utilized for early and reliable prediction of possible major sequelae.
Epitranscriptomics explores how post-transcriptional modifications of RNA transcripts (coding and non-coding) influence the fate and functions of RNA, with consequences on cardiovascular development and diseases. In recent years, the N6-Methyladenosine (m6A) RNA modification was identified as the most abundant epitranscriptomic alteration that plays a role in the regulation of multiple cellular processes. Functional studies revealed that changes in the m6A RNA modification status are involved in mechanisms related to atherosclerosis development and progression of ischemia-reperfusion injury, cardiac remodeling, and fibrosis, but also to neurological disorders, including neurodegenerative diseases and cognitive dysfunction.
The YMCA project aims to explore if the m6A RNA modification in circulating RNAs could be used as biomarker of neurological impairment or death after SCA. Whole blood samples, coming from Luxembourgish patients suffering from cardiac arrest will be used. Furthermore, the project aims to identify and functionally characterize m6A modification in specific coding and non-coding RNAs. To date, clinical studies investigating whether SCA-induced cardiovascular and neurological impairments are reflected through changes in m6A RNA modification of circulating RNAs are lacking. Early detection of such changes may help predict and possibly prevent the occurrence and development of adverse events after SCA and therefore may impact healthcare and improve patient’s outcome.

This project is funded by Fondation COEUR Daniel-Wagner