Elevated blood pressure and cardiac hypertrophy after ablation of the gly96/IEX-1 gene

Stacy L. Sommer, Theresa J. Berndt, Elena Frank, Jeetendra B. Patel, Margaret M. Redfield, Xiangyang Dong, Matthew D. Griffin, Joseph P. Grande, Jan M.A. Van Deursen, Gary C. Sieck, Juan C. Romero, Rajiv Kumar

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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-1α 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-α, and cGMP kinase-1 are increased in gly96/IEX-1-/- mice. Treatment with Nω-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.

Original languageEnglish (US)
Pages (from-to)707-716
Number of pages10
JournalJournal of applied physiology
Volume100
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Apoptosis
  • Elevated blood pressure
  • Lymphoid cells

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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