CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
The heart with prediabetes: intracellular pathway for cardiac apoptosis
SOMMESE L ; ZANUZZI C; PORTIANSKY E; DEDMAN J; KAETZEL M,; MATTIAZZI A; PALOMEQUE J
Foz de Iguazu
Congreso; 1st Panamerican Congress; 2014
Diabetes is usually preceded by impaired glucose tolerance (IGT) or prediabetes and apoptosis in IGT hearts has not been studied. Moreover, CaMKII hyperactivity is a pro-apoptotic event. Thus, we aimed to establish if IGT model fosters an hyperacted of CaMKII linked to cardiac apoptosis via mitochondrial pathway. IGT was induced by a fructose-rich diet (F vs control diet, C, rats or mice), and hearts were subjected to biochemical studies, Ca2+i and reactive oxygen species (ROS) measurements, and mitochondrial swelling experiments. F rats showed increased CaMKII activity (P-CaMKII 91.6±18.3%, Ox-CaMKII 27.75±7.67%, P-Thr17 of PLN 127.6±28.6% and P-Ser2814 of RyR2 42.23±11.25%) and ROS (85.4±28.6%) vs C rats. F rats also presented spontaneous Ca2+ release events (SCRE) unrelated with an enhanced Na+-Ca2+ exchanger activity. Apoptosis increased (ratio Bax/Bcl2 173.6±39.7% and TUNEL positive nuclei) in F vs. C rats. Mitochondria from F rats showed significant more swelling than C mitochondria (DDO 0.34±0.05 CD vs. 0.56±0.03 FRD). F SR-AIP mice (which express a CaMKII inhibitor at the sarcoplasmic reticulum (SR) membranes), showed no SCRE and less apoptosis than their matched F control mice; and F control mice co-treated with tempol (ROS scavenger) also showed no SCRE and less apoptosis than the one induced by fructose alone. Hearts with prediabetes showed increased apoptosis involving CaMKII activation, CaMKII-dependent phosphorylation of SR proteins, increment of SCRE and ROS and mitochondrial damage.