The function and biomarker potential of mitochondrial microRNAs in hypertension

Description du projet

Des biomarqueurs microARN pour l’hypertension

L’hypertension représente la principale cause de maladie cardiovasculaire, affectant près d’un tiers de la population adulte mondiale. Les diagnostics et les traitements n’ayant pas évolués depuis un certain nombre d’années, les scientifiques du projet MITO, financé par l’UE, ont étudié de nouvelles méthodes pour améliorer les soins de santé des patients souffrant d’hypertension. Leur travail sera axé sur la découverte des microARN mitochondriaux dans le sang des sujets atteints d’hypertension. Ces petites molécules régulatrices constituent une source accessible de biomarqueurs et ont été largement utilisées comme cibles thérapeutiques dans des applications cliniques. Les chercheurs sont également intéressés par l’étude du rôle des microARN dans le développement de l’hypertension, ouvrant ainsi la voie pour la découverte de nouvelles thérapies contre l’hypertension.

Objectif

Hypertension is an extreme public health problem affecting nearly one third of the World’s adult population. Most cardiovascular diseases are provoked by hypertension resulting in an estimated 9.4 million deaths every year. Surprisingly, the diagnosis of hypertension has changed very little over the past 100 years - just using a stethoscope definitely needs refining. Furthermore, the epidemic proportion of hypertension worldwide pinpoints the necessity for the discovery of fresh antihypertensive therapies. Thus the main objective of the MITO project is to discover novel methods to improve healthcare of hypertension patients. For this we will investigate the circulating pool of microRNAs (small RNA molecules present in the blood, regulating gene expression) - we hypothesize that particularly mitochondrial microRNAs play a critical role in hypertension development. Easily obtainable in the blood, microRNAs constitute an accessible source of biomarkers and therapeutic targets for clinical application. The research plan envisages three scientific work packages dedicated (1) to the discovery of candidate microRNAs associated with hypertension by using small RNA sequencing in 30 hypertensive patients and 30 controls, (2) the validation of candidate microRNAs in a group of 540 participants (paying attention to sex specificities), and (3) to the functional assessment of the role of microRNAs in hypertension development. While the first two parts of the project will be conducted at the host institution in Luxembourg, functional studies will involve three secondments to partner institutions in Denmark, Germany, and France. A successful outcome will have implications ranging from contributing to satisfy the need for novel methods to stop the progression of hypertension, to a better understanding of the role of microRNAs in hypertension development, to the training of a young East European researcher to pioneer development in a research field just emerging in her home country.