Glycogen Phosphorylase Isoenzyme BB Plasma Concentration Is Elevated in Pregnancy and Preterm Preeclampsia

Abstract

Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from six groups (n=396) were studied: non-pregnant women and pregnant women with normal term delivery, term preeclampsia, term small-for-gestational-age neonates, preterm preeclampsia, and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term cases were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in non-pregnant women (38.7 ng/ml versus 9.2 ng/mL, P<0.001), which remained significant after adjusting for age, race, and parity. Maternal plasma GPBB concentrations did not change throughout gestation. Preterm but not term preeclampsia cases had higher median plasma GPBB concentration than gestational-age-matched normal pregnancy cases (72.6 ng/ml versus 26.0 ng/ml, P=0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases (P<0.01). There is physiologic elevation of plasma GPBB concentration during pregnancy; an increase in maternal plasma GPBB is a novel phenotype of preterm preeclampsia. It is strongly suggested that these changes are attributed to GPBB of placental origin.

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“…Se obtuvieron 8 referencias bibliográficas: 4 relacionadas con las preguntas clínicas, pero sólo 3 resultaron relevantes (el resto se descartó) para el análisis, [1][2][3] pues la cuarta se refirió a una publicación duplicada, con título diferente. 3,4 Las investigaciones se publicaron entre 2012, 2013, 2015 y 2016.…”

“…La isoenzima BB de la fosforilasa de glucógeno (GPBB) no es específica de la gestación (también se encuentra de manera natural en mujeres no embarazadas) ni de la preeclampsia, pues puede detectarse en mujeres con embarazos normales. 1 Esto hace difícil plantear o elaborar una prueba cualitativa, como se expende, con resultado dicotómico positivo versus negativo en sangre capilar.…”

“…Los únicos tres estudios disponibles de GPBB en pacientes embarazadas [1][2][3] reportan concentraciones significativamente mayores en suero al momento del diagnóstico clínico de preeclampsia y del diagnóstico ecográfico de hipotrofia fetal; los autores muestran estos resultados de forma descriptiva, como parte del fenotipo de la preeclampsia clínica y no como una prueba diagnóstica. No se encontraron estudios que incluyan la determinación de GPBB en suero de mujeres embarazadas con otros subtipos de la enfermedad hipertensiva del embarazo, por lo que tampoco se ha comprobado que sea específica de la enfermedad endotelial.…”

Glycogenolysis in Acquired Glioma Resistance to Temozolomide: A Role for the [Ca2+]i-dependent Activation of Na,K-ATPase/ERK1/2 Signaling

“…GPBB converts inactive phosphorylase a into active phosphorylase b in the brain. The median plasma GPBB concentration in patients with high-grade glioma is almost two- to threefold greater than in non-malignant patients, with a cut-off value for the diagnosis of an acute coronary syndrome at 10 ng/ml ( Lee et al, 2012 ). There is no evidence that patients with glioma have an increased risk for ischemic myocardial damage.…”

Novel Invasive and Noninvasive Cardiac-Specific Biomarkers in Obesity and Cardiovascular Diseases

“…151 A high concentration gradient of GP in the sarcoplasmic reticulum compartment allows efflux of GP into the bloodstream through the T-tubule system. 151 Ischemia-induced structural alterations in the cell membrane 151,154 effluxes GPBB into the extracellular fluid. Therefore, the amount of association with the sarcoplasmic reticulum glycogenolysis complex depends primarily on the metabolic state of the myocardium.…”