Genes and pathways regulating aldosterone production: implications for the pathogenesis of primary aldosteronism – BeyondTASKs

Arterial hypertension (HT) represents one of the major risk factors for cardiovascular disease and a major public heaalth problem. Pathogenic mechanisms underlying HT are complex and include genetic and environmental, vascular and hormonal factors. Detection of secondary forms of HT is particularly important since it allows for the targeted management of the underlying disease. Primary aldosteronism (PAL) is the most common form of secondary hypertension, whose prevalence may reach 10% of cases referred to specialized centres, and its diagnosis is important since patients may be cured by surgical or medical treatment. The understanding of the pathogenic mechanisms underlying PAL is essential to allow for the development of new diagnostic tools and biomarkers and may allow to identify new therapeutic targets.
In our research project (BeyondTASKs) we propose to identify new genes and signalling pathways involved in aldosterone biosynthesis in the normal adrenal cortex and in PAL through a strategy that integrates functional genomics, mouse models and studies in patients with PAL, taking advantage of the formidable model represented by Task mutant mice.
Our project, which represents the continuation of our previous ANR GENOPAT HypertenTASK project, will be subdived into four tasks:
1) Management and coordination
2) Study of the transcriptional mechanisms regulating aldosterone production in the adrenal cortex
3) Investigation of mechanisms leading to hyperaldosteronism in the Task3-null mouse model
4) Investigation of the genetic and genomic determinants of PAL in humans

We expect that the results produced by our project will considerably broaden our knowledge in the field of the regulation of aldosterone production in physiological and pathological conditions and discover new therapeutic targets.