Diabetes with or without the presence of
hypertension damages the heart. However, there is currently a lack of information about these associated pathologies and the alteration of linked
proteins. For these reasons, we were interested in the potential synergistic interaction of diabetes and
hypertension in the heart, focusing on the
proteome characterization of the pathological phenotypes and the associated hypertrophic response. We treated normotensive and spontaneously hypertensive (SHR) rats with either
streptozotocin or vehicle. After 22weeks, type-I diabetic (DM1), SHR, SHR/DM1 and control left-ventricles were studied using proteomic approaches. Proteomics revealed that long-term DM1, SHR and SHR/DM1 rats exhibited 24, 53 and 53 altered
proteins in the myocardia, respectively. DM1 myocardium showed over-expression of apoptotic and cytoskeleton
proteins, and down-regulation of anti-apoptotic and mitochondrial metabolic
enzymes. In both SHR and SHR/DM1 these changes were exacerbated and
free fatty-acid (FFA) ß-oxidation
enzymes were additionally decreased. Furthermore, SHR/DM1 hearts exhibited a misbalance of specific pro-hypertrophic, anti-apoptotic and mitochondrial
ATP-carrier factors, which could cause additional damage. Differential
proteins were validated and then clustered into different
biological pathways using bioinformatics. These studies suggested the implication of FFA-
nuclear receptors and hypertrophic factors in these pathologies. Although key ß-oxidation
enzymes were not stimulated in DM1 and hypertensive hearts,
peroxisome proliferator-activated receptors-α (PPARα) were potentially activated for other responses. In this regard, PPARα stimulation reduced
hypertrophy and pro-hypertrophic factors such as
annexin-V in high-
glucose and
angiotensin-II induced cardiomyocytes. Thus, activation of PPARα could reflect a compensatory response to the metabolic-shifted, apoptotic and hypertrophic status of the hypertensive-
diabetic cardiomyopathy.