title: Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene.
abstract: gly96/IEX 1 is a growth- and apoptosis-regulating, immediate early gene that is widely expressed in epithelial and vascular tissues. In vascular tissues, expression of the gene is induced by mechanical stretch, and overexpression of the gene prevents injury-induced vascular smooth muscle hypertrophy and neointimal hyperplasia. We now show that deletion of the gly96/IEX-1 gene in mice is associated with development of elevated blood pressure, cardiac hypertrophy, and diminished fractional shortening of the left ventricle. Systolic blood pressure in conscious male gly96/IEX-1-/- mice is 20-25 mmHg higher than in gly96/IEX-1+/+ mice. Serum and/or urine concentrations of sodium, potassium, creatinine, angiotensin II, corticosterone, aldosterone, epinephrine, norepinephrine, prostaglandin E2, thromboxane B2, prostaglandin-6-keto-1alpha, nitrites and nitrates, cAMP, and cGMP are normal in gly96/IEX-1-/- mice. Alterations in dietary sodium intake do not alter blood pressure in gly96/IEX-1-/- mice. Aortic mRNAs for endothelial nitric oxide synthase, guanylate cyclase-alpha, and cGMP kinase-1 are increased in gly96/IEX-1-/- mice. Treatment with Nomega-nitro-L-arginine methyl ester or L-arginine does not alter blood pressure in gly96/IEX-1-/- mice. Gly96/IEX-1-/- mice respond to infused sodium nitroprusside with decrements in blood pressure similar to those seen in wild-type littermate mice. In contrast to gly96/IEX-1 transgenic mice that have abnormalities in immune function, gly96/IEX-1-/- mice have normal lymphoid tissue architecture and a normal complement of T and B cells in lymphoid tissues. Ablation of the gly96/IEX-1 gene results in hypertension and cardiac hypertrophy, suggesting a novel role for this gene in cardiovascular physiology.
authors.affiliation: Department of Internal Medicine, MS 1-120, Mayo Clinic Rochester, Mayo College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Sommer
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Berndt
authors.forename: Elena
authors.initials: E
authors.lastname: Frank
authors.forename: Jeetendra B
authors.initials: JB
authors.lastname: Patel
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Dong
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Griffin
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Grande
authors.forename: Jan M A
authors.initials: JM
authors.lastname: van Deursen
authors.forename: Gary C
authors.initials: GC
authors.lastname: Sieck
authors.forename: Juan C
authors.initials: JC
authors.lastname: Romero
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001011:Aorta / Q000201:enzymology; D001794:Blood Pressure; D006332:Cardiomegaly / Q000201:enzymology / Q000235:genetics*; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D017874:Immediate-Early Proteins / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000201:enzymology / Q000235:genetics
chemical_list: D000959:Antihypertensive Agents; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D009599:Nitroprusside; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse; D006162:Guanylate Cyclase