Sodium myo-inositol cotransporter 1 (SMIT1): a new player to prevent left ventricular remodelling?

Speaker: Dr Alice Marino (UCL and Institut de Recherche Expérimentale et Clinique, Belgium)

Title: Sodium myo-inositol cotransporter 1 (SMIT1): a new player to prevent left ventricular remodelling?

Hosts: Dr Anna Zoccarato

Abstract:

Sodium myo-inositol cotransporter-1 (SMIT1) belongs to the sodium-glucose cotransporter family and accounts for intracellular accumulation of myo-inositol. SMIT1 is expressed in the heart, where its function remains unknown.

Here, we demonstrate the contribution of SMIT1 in pathological hypertrophic cardiac remodelling and the progression to heart failure, using a mouse model of pressure overload induced by transverse aortic constriction.

We found that aortic banding failed to induce systolic dysfunction, cardiac hypertrophy and fibrosis in mice lacking SMIT1 (Smit1^-/-), in contrast to wild type controls. SMIT1 genetic deletion reduced cardiac O-GlcNAcylation, which normally increases following hemodynamic stress, and restored ions homeostasis preventing the resulting pro-hypertrophic transcriptional reprograming.

This work provides important insights into the role of SMIT1 at the onset of heart failure, opening new avenues for potential therapeutic strategy to prevent or treat pathological hypertrophy and heart failure.

Bio: 

During the past eleven years, I have been interested in understanding the mechanisms that confer protection against cardiac diseases, such as ischemia, heart failure, atherosclerosis and thrombosis.

I obtained my PhD in Clinical Pathophysiology and Drug Science at the University of Pisa (Italy) in 2015. After my graduation, I pursued two postdocs at Weill Cornell Medicine (New York, USA) between 2015 and 2019, where I investigated cardioprotective mechanisms against myocardial ischemia/reperfusion, heart failure, diabetic cardiomyopathy, and atherosclerosis.

Since October 2019, I work in the laboratory of Prof. Beauloye, in the CARD unit at IREC UCLouvain in Belgium, where my research focuses on the role of sodium-glucose co-transporters in the context of healthy and diseased hearts. Specifically, I aim to unravel the impact of SMIT1, a transporter of myo-inositol, in cardiac fibrosis, hypertrophy and left ventricular remodeling.