PHACTR1 modulates vascular compliance but not endothelial function: a translational study.
Wood A., Antonopoulos A., Chuaiphichai S., Kyriakou T., Diaz R., Al Hussaini A., Marsh A-M., Sian M., Meisuria M., McCann G., Rashbrook VS., Drydale E., Draycott S., Polkinghorne MD., Akoumianakis I., Antoniades C., Watkins H., Channon KM., Adlam D., Douglas G.
IntroductionThe non-coding locus at 6p24 located in intron 3 of PHACTR1 has consistently been implicated as a risk allele in myocardial infarction and multiple other vascular diseases. Recent murine studies have identified a role for Phactr1 in the development of atherosclerosis. However, the role of PHACTR1 in vascular tone and in vivo vascular remodelling has yet to be established. The aim of this study was to investigate the role of PHACTR1 in vascular function.Methods and resultsProspectively recruited coronary artery disease (CAD) patients undergoing bypass surgery and retrospectively recruited spontaneous coronary artery dissection (SCAD) patients and matched healthy volunteers were genotyped at the PHACTR1 rs9349379 locus. We observed a significant association between the PHACTR1 loci and changes in distensibility in both the ascending aorta (AA = 0.0053 ± 0.0004, AG = 0.0041 ± 0.003, GG = 0.0034 ± 0.0009, P ConclusionIn conclusion, we have shown a role for PHACTR1 in arterial compliance across multiple vascular beds. Our study suggests that PHACTR1 has a key structural role within the vasculature.