Ablation of the Hypertension Candidate Gene ATP2B1 Results in Increased Blood Pressure and Cardiac Hypertrophic Remodeling. American Heart Association Scientific Sessions 2014-Abstract 13798

Introduction: Hypertension is a major risk factor for cardiac hypertrophy and heart failure. Genome wide association studies have recently identified single nucleotide polymorphisms in ATP2B1, the gene encoding the calcium extrusion pump, plasma membrane calcium ATPase (PMCA1), as having a strong association with hypertension risk.Hypothesis: PMCA1 plays an important role in regulation of blood pressure and protection against hypertension and cardiac hypertrophy.Aims: We aim to examine whether there is a functional link between PMCA1 and blood pressure regulation, and the development of hypertension. And to determine the impact this link may have on cardiac structure and function.Methods and Results: To study the role of PMCA1 we generated a global PMCA1 heterozygous knockout mouse (PMCA1Ht). PMCA1Ht mice had 46% to 52% reduction in PMCA1 protein expression compared to the WT, in aorta, heart, kidney and brain.To study the mice under hypertensive stress conditions, 3 month old PMCA1Ht and wild type (WT) mice were infused via minipump with angiotensin II (1mg/Kg/daily) or water as a control. Upon angiotensin treatment, PMCA1Ht mice showed a significantly greater increase in systolic (62.24±3.05 mmHg) and diastolic pressure (52.68±4.67 mmHg), in comparison to the WT (33.37±2.91 mmHg and 23.94±4.56 mmHg, respectively), P