Grant: Travel Awards - Institute Community Support

Cardiovascular disease is the leading cause of death and disability in the world. Though extensive research has led to advanced treatments, most increase the survival rate without improving the quality of life. Thus further research on novel molecular pathways in cardiac physiology is imperative to tackle the progression of chronic heart failure. Smoothelin-like 1 (SMTNL1) protein is a novel regulator of vascular homeostasis and belongs to smoothelin family of muscle proteins. The deletion of SMTNL1 provides an exercise-adapted phenotype in muscle cells and improves cardiovascular performance in the absence of any exercise activity. Robust compensatory mechanisms involving SMTNL1 may efficiently counterbalance pressure-overload-induced impairment in cardiac function. The project examined the pathological cardiac remodeling and disease progression in response to pressure-overload-induced biomechanical stress (i.e., hypertension) in two well defined models of HF: (1) transverse aortic constriction (TAC) model induced HF and (2) angiotensin (Ang)-II infusion-induced HF model with diastolic dysfunction but with preserved contractility. Ten-week old male KO and WT (n=10/group) mice underwent TAC or Ang II infusion (1.5mg/kg/day). Sham-operated mice and vehicle administered mice served as the control groups, respectively. At week 0 and after 4 weeks of pressure-overload, mice were subjected to echocardiographic (ECG) analysis of heart function. Mice were terminated and tissues harvested for further molecular analysis. ECG analysis of naïve KO mice before undergoing pressure-overload induction shows improved ejection fraction and cardiac output when compared to the WT counterparts. The proposed study will help us to elucidate the pathophysiological role of SMTNL1 protein in the regulation of cardiac hemodynamics in pre-clinical models of heart failure, which aids in the development of SMTNL1 based therapeutics or diagnostic markers in the field of cardiovascular disease.