Grant: Travel Awards - Institute Community Support

Heart failure (HF) is the common final outcome for most patients with cardiovascular disease. Approximately 600,000 Canadians are identified to be living with heart failure (1.5% prevalence) in 2016. Over the past decade, HF with preserved ejection fraction (HFpEF) characterized by the impairment of relaxation phase of heart, mainly due to vessel dysfunction; has gained increasing prevalence. It currently accounts for ~50% HF diagnoses. However, no successful therapeutics are available for the treatments of HFpEF patients. Thus, further research on novel molecular pathways in cardiac physiology is imperative to tackle the progression of HFpEF. Smoothelin-like 1 (SMTNL1) protein is a novel regulator of blood vessel function, including vascular tone and blood flow, blood vessel (endothelial) barrier function, inflammatory responses, transendothelial migration of circulating immune cells, and wound repair. We recently showed development of impairment in relaxation of heart with the deletion of SMTNL1 in young male mice. Echocardiographic (ECG) and pressure-volume loop measurements were carried out in 3-, 12-and 18-month old male and female SMTNL1 knockout (KO) mice to study the effect of age and sex on relaxation with SMTNL1 deficiency. The 129S6 wildtype (WT) background strain at each age point served as the control group. ECG analysis of KO mice showed normal contractile function when compared to the WT counterparts with ageing. However, the PV loop data revealed impaired relaxation in male cohort at all age points while female KO group developed it only at post-menopausal age of 18-months, compared to their control WT counterparts. The study will help us to elucidate the sex-dimorphic and pathophysiological role of SMTNL1 protein in the regulation of cardiac hemodynamics in pre-clinical models of heart failure and aid in the development of SMTNL1 based therapeutics or diagnostic markers in the field of HFpEF.