Remodeling of Glucose Metabolism Precedes Pressure Overload-Induced Left Ventricular Hypertrophy: Review of a Hypothesis

Author:

Kundu Bijoy K.,Zhong Min,Sen Shiraj,Davogustto Giovanni,Keller Susanna R.,Taegtmeyer Heinrich

Abstract

When subjected to pressure overload, the ventricular myocardium shifts from fatty acids to glucose as its main source for energy provision and frequently increases its mass. Here, we review the evidence in support of the concept that metabolic remodeling, measured as an increased myocardial glucose uptake using dynamic positron emission tomography (PET) with the glucose analogue 2-deoxy-2-[18F]fluoro-D-glucose (FDG), precedes the onset of left ventricular hypertrophy (LVH) and heart failure. Consistent with this, early intervention with propranolol, which attenuates glucose uptake, prevents the maladaptive metabolic response and preserves cardiac function in vivo. We also review ex vivo studies suggesting a link between dysregulated myocardial glucose metabolism, intracellular accumulation of glucose 6-phosphate (G6P) and contractile dysfunction of the heart. G6P levels correlate with activation of mTOR (mechanistic target of rapamycin) and endoplasmic reticulum stress. This sequence of events could be prevented by pretreatment with rapamycin (mTOR inhibition) or metformin (enzyme 5′-AMP-activated protein kinase activation). In conclusion, we propose that metabolic imaging with FDG PET may provide a novel approach to guide the treatment of patients with hypertension-induced LVH.

Publisher

S. Karger AG

Subject

Pharmacology (medical),Cardiology and Cardiovascular Medicine

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