title: The role of GRIP1 and ephrin B3 in blood pressure control and vascular smooth muscle cell contractility.
abstract: Several erythropoietin-producing hepatocellular receptor B family (EPHB) and their ligands, ephrinBs (EFNBs), are involved in blood pressure regulation in animal models. We selected 528 single nucleotide polymorphisms (SNPs) within the genes of EPHB6, EFNB2, EFNB3 and GRIP1 in the EPH/EFN signalling system to query the International Blood Pressure Consortium dataset. A SNP within the glutamate receptor interacting protein 1 (GRIP1) gene presented a p-value of 0.000389, approaching the critical p-value of 0.000302, for association with diastolic blood pressure of 60,396 individuals. According to echocardiography, we found that Efnb3 gene knockout mice showed enhanced constriction in the carotid arteries. In vitro studies revealed that in mouse vascular smooth muscle cells, siRNA knockdown of GRIP1, which is in the EFNB3 reverse signalling pathway, resulted in increased contractility of these cells. These data suggest that molecules in the EPHB/EFNB signalling pathways, specifically EFNB3 and GRIP1, are involved blood pressure regulation.
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Zenghui
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Luo
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Junzheng
authors.initials: J
authors.lastname: Peng
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Raelson
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Georg B
authors.initials: GB
authors.lastname: Ehret
authors.affiliation: Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Munroe
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Ekatherina
authors.initials: E
authors.lastname: Stoyanova
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Cloutier
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: W Edward
authors.initials: WE
authors.lastname: Bradley
authors.affiliation: Institute of Cardiology, First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, 310003, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Institute of Cardiology, First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, 310003, China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Shen
authors.affiliation: Institute of Cardiology, First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, 310003, China.
authors.forename: Shenjiang
authors.initials: S
authors.lastname: Hu
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.|Nephrology Service, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D036389:Ephrin-B3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D036389:Ephrin-B3; C491310:GRIP1 protein, human; D009419:Nerve Tissue Proteins