Abstract
Diabetic cardiomyopathy (DCM) is one of the most harmful diseases with high morbidity and mortality rates. However, the underlying pathological mechanism of the disorder still remains unclear. The purpose of our study was to identify differentially expressed proteins associated with DCM. C57BLKS/J db/db (diabetes mellitus group - DM group) and db/m mice (normal control group - NC group) were acclimated in cages for 15 weeks. The general state was recorded. After 15 weeks, the heart tissues were used for histological examination. In addition, quantitative mass spectrometry using isobaric tags for relative and absolute quantitation (iTRAQ) was used to identify differentially expressed proteins in the heart tissues. SEQUEST software was used to identify proteins with data derived from liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectra by searching ipi.MOUSE.v3.72.REVERSED. fasta database. Expert Protein Analysis System (ExPASy) was used to calculate the theoretical parameters. One upregulated protein (sorbin and SH3 domain containing 2 - Sorbs2) and 1 downregulated protein (myosin-3) was measured by western blot to validate the iTRAQ data. The mice in the NC group were active and grew well, while the mice in the DM group presented with obvious polydipsia, polyphagia and polyuria. The results of histological examination revealed that, compared to the NC group, the DM group showed significant myocardial hypertrophy and myofiber disarray accompanied by damaged nuclei. A total of 73 differentially expressed proteins were identified, including 44 upregulated and 29 downregulated proteins. Western blot analysis confirmed that the expression of Sorbs2 was significantly increased (p < 0.01), while the expression of myosin-3 was statistically decreased in the DM group compared to the NC group (p < 0.05). These results suggest that DCM shows differences in its proteomics compared to normal controls. Our quantitative proteomic analysis may provide a new insight into the distinct molecular profile of DCM.
Highlights
The number of patients with diabetes mellitus (DM) has been increasing worldwide at an alarming pace for the past 2 decades
The results of histological examination revealed that, compared to the normal control (NC) group, the DM group showed significant myocardial hypertrophy and myofiber disarray accompanied by damaged nuclei
Western blot analysis confirmed that the expression of Sorbs[2] was significantly increased (p < 0.01), while the expression of myosin-3 was statistically decreased in the DM group compared to the NC group (p < 0.05)
Summary
The number of patients with diabetes mellitus (DM) has been increasing worldwide at an alarming pace for the past 2 decades. These patients are predisposed to serious cardiovascular complications, including heart failure (HF), causing mortality and morbidity.[1] The development of diabetic cardiomyopathy (DCM) is a prominent contributing factor to HF.[2] The term DCM was first introduced by Rubler et al, and it is characterized by adverse structural and functional changes in the myocardium and coronary vasculature in the absence of coronary artery disease (CAD) and hypertension.[2,3,4] Among the diabetic population, the prevalence of DCM has been estimated between 30% and 60%.5,6. The underlying pathological mechanism of the disorder still remains unclear
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