AbstractBackground: ATP-sensitive potassium channels are ATP sensitive pores that are found in vascular smooth muscle cells and play an important role in regulating vascular function. They are also expressed in blood but their relationship with vascular function is unknown. This study aims to investigate the previously unknown relationship between levels of KATP channels in blood and vascular function in normal healthy subjects.
Methods: Blood samples were obtained and vascular function was assessed by carrying out four non-invasive tests in 50 normal healthy subjects. The levels of KATP channels were determined by measuring levels of mRNA subunits, Kir6.1/SUR2B, using real time reverse transcription polymerase chain reaction (RT-PCR) test while vascular function was assessed using (i) iontophoresis with laser Doppler flowmetry (LDF); (ii) post-occlusive reactive hyperaemia test (PORH) in the skin microvessels; (iii) pulse wave analysis (PWA) for arterial stiffness and (iv) flow-mediated dilation (FMD) in the macrovessels.
Results: This study showed that Kir6.1 but not SUR2B, mRNA can be detected in human blood. In addition, acetylcholine (ACH) (r=-0.579, p<0.001, n=40) and PORH (r= 0.366 p=0.020, n=40) correlated with Kir6.1 mRNA levels. No correlation was noted in brachial artery FMD (r=0.181, p=0.264, n=40) with Kir6.1 mRNA levels. Further analysis demonstrated gender specific differences where males showed statistically significant correlation between Kir6.1 mRNA levels and ACH (r=-0.561, p=0.005, n=23) as well as PORH (r= 0.418, p= 0.047, n= 23) but in females significant correlation was only seen between Kir6.1 mRNA levels and ACH (r=-0.628, p=0.007, n=17) but not PORH.
Conclusion: The mRNA Kir6.1subunit levels in blood showed significant relationship with microvascular function. However, further studies are required to investigate the differences in direction of correlation between ACH and Kir6.1 mRNA levels (negative correlation) as well as PORH and Kir6.1 mRNA levels (positive correlation). Levels of KATP in blood could potentially be used as blood marker for vascular function in vivo.
|Date of Award||2013|
|Supervisor||Faisel Khan (Supervisor) & Aleksandar Jovanovic (Supervisor)|