Abstract 1370: Biochemical and Proteomic Approach to the Study of the Experimental Diabetic Myocardium
Background: Diabetes mellitus (DM) may affect directly the heart. The acute effect of DM on the myocardium has been described. However, the effect of long-standing DM and of coexisting hypertension (HT) has not been studied.
Aims: To study the myocardium of long-standing type I DM (DM1), HT and both pathologies (DM1/HT) analysing changes in protein expression by proteomic techniques.
Methods: Normotensive and HT rats were injected 50 mg/kg streptozotocin to develop DM1. Vehicle-administrated rats were used as control. After 22 weeks, rats were killed and their left ventricles isolated for histological, biochemical, and proteomic (DIGE) and mass spectrometry assays.
Results: DM1 myocardium showed hypertrophy, fibrosis and apoptosis, with over-expression/activation of pro-fibrotic (transforming growth factor-β, connective tissue growth factor, linked transcription factors p-Smad3/4 and AP-1), and pro-apoptotic (Fas, Fas L, Bax, and cleaved caspase-3) factors. HT myocardium shared these features and showed, additionally, inflammatory cell infiltrate, with NF-κB activation, and expression of monocyte chemoattractant protein-1, and interleukins-1β and -6, which were absent in DM1. DM1/HT rats showed a similar pro-fibrotic and pro-apoptotic state without inflammatory response. By a proteomic approach we found 32, 63 and 70 proteins altered in the myocardium of DM1, HT and DM1/HT rats, respectively (p<0.05). Among these, DM1 myocardium presented over-expression of cytoskeleton (Desmin) and apoptotic (Anexin-5) proteins, and down-regulation of anti-apoptotic (HSPs), mitochondrial (Malate deshydrogenase) and aminoacid (Bcat-2) metabolic enzymes. HT and DM1/HT rats showed similar changes and additionally, a diminution in fatty acid (Acyl CoA desHydrogenase) and sugar (Pyr-Kinase) catabolic enzymes.
Conclusions: Long-standing DM1 is associated to myocardial fibrosis and apoptosis and changes in the expression of mitochondrial and aminoacid metabolic enzymes. When HT coexists, there is also a reduction of the expression of sugar and fatty acid metabolic enzymes. These findings may be related to the myocardial dysfunction observed in DM1 and HT. Further study is needed to confirm if they play a causative role.