title: 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.
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.
authors: Tufts Medical Center, Molecular Cardiology Research Institute, 800 Washington Street, Box 80, Boston, MA 02111. rblanton@tuftsmedicalcenter.org.
authors: Robert M
authors: RM
authors: Blanton
authors: Eiki
authors: E
authors: Takimoto
authors: Mark
authors: M
authors: Aronovitz
authors: Robrecht
authors: R
authors: Thoonen
authors: David A
authors: DA
authors: Kass
authors: Richard H
authors: RH
authors: Karas
authors: Michael E
authors: ME
authors: Mendelsohn
mesh_terms: D000367:Age Factors; D000818:Animals; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D016350:Leucine Zippers / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016277:Ventricular Function, Left
chemical_list: D062965:Cyclic GMP-Dependent Protein Kinase Type I
keywords: Hypertension; Left ventricular hypertrophy; Protein kinase G.
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