Mice Lacking Hypertension Candidate Gene ATP2B1 in Vascular Smooth Muscle Cells Show Significant Blood Pressure Elevation
- 1 April 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 59 (4), 854-860
- https://doi.org/10.1161/hypertensionaha.110.165068
Abstract
We reported previously that ATP2B1 was one of the genes for hypertension receptivity in a large-scale Japanese population, which has been replicated recently in Europeans and Koreans. ATP2B1 encodes the plasma membrane calcium ATPase isoform 1, which plays a critical role in intracellular calcium homeostasis. In addition, it is suggested that ATP2B1 plays a major role in vascular smooth muscle contraction. Because the ATP2B1 knockout (KO) mouse is embryo-lethal, we generated mice with vascular smooth muscle cell-specific KO of ATP2B1 using the Cre-loxP system to clarify the relationship between ATP2B1 and hypertension. The KO mice expressed significantly lower levels of ATP2B1 mRNA and protein in the aorta compared with control mice. KO mice showed significantly higher systolic blood pressure as measured by tail-cuff method and radiotelemetric method. Similar to ATP2B1, the expression of the Na + -Ca 2+ exchanger isoform 1 mRNA was decreased in vascular smooth muscle cells of KO mice. However, ATP2B4 expression was increased in KO mice. The cultured vascular smooth muscle cells of KO mice showed increased intracellular calcium concentration not only in basal condition but also in phenylephrine-stimulated condition. Furthermore, phenylephrine-induced vasoconstriction was significantly increased in vascular rings of the femoral artery of KO mice. These results suggest that ATP2B1 plays important roles in the regulation of blood pressure through alteration of calcium handling and vasoconstriction in vascular smooth muscle cells.Keywords
This publication has 27 references indexed in Scilit:
- Caloxin 1b3: A novel plasma membrane Ca2+-pump isoform 1 selective inhibitor that increases cytosolic Ca2+ in endothelial cellsCell Calcium, 2010
- Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to HypertensionHypertension, 2010
- Blood Pressure and Hypertension Are Associated With 7 Loci in the Japanese PopulationCirculation, 2010
- Genetic variations in ATP2B1, CSK, ARSG and CSMD1 loci are related to blood pressure and/or hypertension in two Korean cohortsJournal of Human Hypertension, 2009
- Orai1, a critical component of store-operated Ca2+ entry, is functionally associated with Na+/Ca2+ exchanger and plasma membrane Ca2+ pump in proliferating human arterial myocytesAmerican Journal of Physiology-Cell Physiology, 2009
- T-type Ca2+ Channels Promote Oxygenation-induced Closure of the Rat Ductus Arteriosus Not Only by Vasoconstriction but Also by Neointima FormationOnline Journal of Public Health Informatics, 2009
- Genome-wide association study of blood pressure and hypertensionNature Genetics, 2009
- Identification of Hypertension-Susceptibility Genes and Pathways by a Systemic Multiple Candidate Gene Approach: The Millennium Genome Project for HypertensionHypertension Research, 2008
- Superoxide Mediates Angiotensin II–Induced Influx of Extracellular Calcium in Neural CellsHypertension, 2005
- Targeted Ablation of Plasma Membrane Ca2+-ATPase (PMCA) 1 and 4 Indicates a Major Housekeeping Function for PMCA1 and a Critical Role in Hyperactivated Sperm Motility and Male Fertility for PMCA4Online Journal of Public Health Informatics, 2004