Investigation into the role of omega-3 fatty acids and structural analogues on Kv7 channel function and vasodilator mechanisms (Ms Kamila Behnam)

Improved cardiovascular health is often attributed to the consumption of the omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

These essential fatty acids reduce blood pressure in the population and to a greater extent in patients with systolic hypertension.

Hypertension is the largest risk factor in global burden of disease and is uncontrolled by current therapy in up to 40% of patients.

Recently n-3 PUFAs have been shown to directly activate Kv7.1 channels in cardiac myocyte cells via an electrostatic mechanism.

Kv7.1, Kv7.4 and Kv7.5 are all expressed in vascular tissue and contribute to regulation of vascular tone, flow and blood pressure.

Our preliminary data suggest that n-3 PUFAs, and certain structural analogues, evoke vascular relaxation by Kv7 dependent mechanisms.

In this study we propose to elucidate the subtype(s) of Kv7 and auxiliary KCNE subunits activated by n-3 PUFAs in vascular tissue and the mechanism by which n-3 PUFAs activate Kv7 channels.

Understanding this will allow us to understand the pharmacophore of n-3 PUFA to be optimised to activate specific vascular Kv7 channel subtypes. Thus, this work aims to ultimately identify lead compounds for the development of new anti-hypertensive agents.