This project will investigate a novel drug combination therapy that has potential benefits in heart failure treatment by targeting Na+-K+ pump function.
We are interested to invite PhD students join our group at the Kolling Medical Research Institute, studying in a topic of "a novel combination drug therapy for heart disease".
Background: A raised intracellular Na+ concentration in cardiac myocytes plays an important role in the mechanisms that perpetuate the progression from an initial myocardial insult to the heart failure syndrome, and, conversely, neurohormonal blockade of proven clinical efficacy stimulates Na+ export mediated by the Na+-K+ pump. We have reported that β3 adrenergic (β3 AR) agonists, drugs developed for non-cardiovascular purposes, stimulate the Na+-K+ pump. β3 AR agonists are promising candidates for the treatment of heart failure, but its downstream interaction with aldosterone has the theoretical potential of reducing or negating a beneficial β3 AR-mediated Na+-K+ pump stimulation or even converting it to harmful pump inhibition.
Experimental approach: Effects of a β3 AR agonist on oxidative molecular modification and activity of the Na+-K+ pump will be studied in isolated cardiac myocytes on a background of oxidative signalling induced by aldosterone activation. We will examine if an aldosterone antagonist has additive effects on signalling pathways and oxidative Na+-K+ pump inhibition of cardiac myocytes when co-administered with a beta3 AR agonist to rabbits with/without heart failure. We will determine whether a co-administration of aldosterone antagonists and beta3 AR agonists prescribed in patients alters the clinical indices of heart failure.
Outcome and significance: This study may provide a better treatment with improved outcome by add-on of already available drugs in heart failure.
The candidate will gain experience in cellular physiology, molecular biology, animal handling and surgery, medical treatment strategies and development. Interested students are asked to apply for all available funding (eg. APA, UPA, Heart Foundation, Heart Research Australia etc.). The potential supervisors will help with this process.
The opportunity ID for this research opportunity is 692