Mutation of the protein kinase i alpha leucine zipper domain produces hypertension and progressive left ventricular hypertrophy: A novel mouse model of age-dependent hypertensive heart disease

Robert M. Blanton, Eiki Takimoto, Mark Aronovitz, Robrecht Thoonen, David A Kass, Richard H. Karas, Michael E. Mendelsohn

Research output: Contribution to journalArticle

Abstract

Hypertensive heart disease causes significant mortality in older patients, yet there is an incomplete understanding of molecular mechanisms that regulate age-dependent hypertensive left ventricular hypertrophy (LVH). Therefore, we tested the hypothesis that the cGMP-dependent protein kinase G I alpha (PKGIα;) attenuates hypertensive LVH by evaluating the cardiac phenotype in mice with selective mutations of the PKGIα; leucine zipper domain. These leucine zipper mutant (LZM) mice develop basal hypertension. Compared with wild-type controls, 8-month-old adult LZM mice developed increased left ventricular end-diastolic pressure but without frank LVH. In advanced age (15 months), the LZM mice developed overt pathological LVH. These findings reveal a role of PKGIα; in normally attenuating hypertensive LVH. Therefore, mutation of the PKGIα; LZ domain produces a clinically relevant model for hypertensive heart disease of aging.

Original languageEnglish (US)
Pages (from-to)1351-1355
Number of pages5
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume68
Issue number11
DOIs
StatePublished - Nov 2013

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Cyclic GMP-Dependent Protein Kinase Type I
Leucine Zippers
Left Ventricular Hypertrophy
Protein Kinases
Heart Diseases
Hypertension
Mutation
Blood Pressure
Phenotype
Mortality

Keywords

  • Hypertension
  • Left ventricular hypertrophy
  • Protein kinase G

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Mutation of the protein kinase i alpha leucine zipper domain produces hypertension and progressive left ventricular hypertrophy : A novel mouse model of age-dependent hypertensive heart disease. / Blanton, Robert M.; Takimoto, Eiki; Aronovitz, Mark; Thoonen, Robrecht; Kass, David A; Karas, Richard H.; Mendelsohn, Michael E.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 68, No. 11, 11.2013, p. 1351-1355.

Research output: Contribution to journalArticle

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