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[OP.2C.01] THE ROLE OF PMCA1 IN HYPERTENSION AND ARRHYTHMIA SUSCEPTIBILITY IN RELATION TO AGEING

Objective: Heart failure prevalence increases with age, from less than 1% in 20–39 year olds to over 20% in those aged over 80. Problems posed by the ageing population means heart failure prevalence is expected to continue rising. Therefore understanding mechanisms involved age-associated cardiovascular changes is vital to conquer the growing epidemic. Multiple GWAS have shown Atp2b1, plasma membrane Ca2+ ATPase 1 (PMCA1), to have a strong genetic association with hypertension. Furthermore, we have previously shown altered PMCA1 expression results in age-associated elevated blood pressure. High blood pressure is a known arrhythmia risk factor, with hypertensive patients having an increased risk of morbidity and mortality associated with arrhythmic development. Therefore using transgenic animal models we aim to investigate a potentially novel link between age-associated hypertension and heart rhythm changes in relation to altered PMCA1 expression. Design and method: The role of PMCA1 in heart rhythm stability was assessed in cardiomyocyte-specific knockout mice (PMCA1CKO) at 3 months of age and PMCA1 heterozygous null mice (PMCA1Ht) at 3 and 18 months of age (aged PMCA1CKO animals are not viable). Heart rhythm stability was determined using in vivo electrocardiography and arrhythmia susceptibility tested using programmed electrical stimulation. To confirm PMCA1 is involved in age-associated hypertension, conscious blood pressure of young and aged PMCA1Ht animals was measured using the tail-cuff method. Results: At 3 months, old PMCA1CKO mice exhibit abnormal heart rhythms, with prolonged QT and JT intervals as well as increased susceptibility to arrhythmic events. However, PMCA1Ht animals at this age shown a normal heart rhythm phenotype compared to controls. Further investigation looking at the effect of ageing on arrhythmia susceptibility shown while aged PMCA1HTt display age associated hypertension their heart rhythm remains comparable to controls. Conclusions: Our findings show that PMCA1 is involved in two of the central features of heart failure arrhythmia development and hypertension. However, the role of PMCA1 in these two areas are cardiophysiology appear to be unrelated and while the hypertension phenotype appears to be affected by ageing, the effect of ageing in relation to the gene's role in heart rhythm stability remains unclear.