Key result
Mutation of the PKGIα leucine zipper domain in mice produced basal hypertension, increased LV end-diastolic pressure at 8 months, and overt pathological LV hypertrophy at 15 months.
Why the study?
Does mutation of the PKGIα leucine zipper domain cause age-dependent hypertensive left ventricular hypertrophy in mice?
Does mutation of the PKGIα leucine zipper domain cause age-dependent hypertensive left ventricular hypertrophy in mice?
Mutation of the PKGIα leucine zipper domain in mice produces a clinically relevant model for age-dependent hypertensive heart disease and left ventricular hypertrophy.
Provides a mouse model of age-dependent hypertensive LVH; leaves open PKGIα leucine zipper relevance to human disease.
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.
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Blanton et al. (2013) studied Hypertensive heart disease and left ventricular hypertrophy. Mutation of the PKGIα leucine zipper domain vs. Wild-type controls was evaluated on Cardiac phenotype including left ventricular end-diastolic pressure and left ventricular hypertrophy. Mutation of the PKGIα leucine zipper domain in mice produced basal hypertension, increased LV end-diastolic pressure at 8 months, and overt pathological LV hypertrophy at 15 months.
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