Implication of adrenergic receptor Beta-3 on cardiac glucose metabolism during Heart Failure

With an estimated number of 37,7 millions people affected worldwide and a high mortality, heart failure (HF) represents a major public health problem. The beta-3 adrenergic receptors (?3AR) are expressed in human cardiac contractile cells. In the past few years, our group and others showed that by reducing oxidative stress ?3AR confer protection against cardiac fibrosis and hypertrophic remodeling, pathophysiological traits associated with the progression of HF.

This project aims to test the hypothesis that the protective role of ?3AR in reducing oxidative stress is mediated by an increase of the pentose phosphate pathway. This pathway generates NADPH, a molecule used by the cell for detoxification, thus reducing oxidative stress. This hypothesis will be tested in dynamic conditions by metabolic flux analysis (MFA) on cardiac tissues presenting a specific expression of the human ?3AR.

As ?3AR agonists are already used in urology clinical practice, the identification of a new protective mechanism mediated by ?3AR effects on metabolism will offer novel and immediate perspectives in the treatment of HF patients.

Faculty Supervisor:

Christine Des Rosiers

Student:

Partner:

Université Catholique de Louvain

Discipline:

Life Sciences

Sector:

Education

University:

Université de Montréal

Program: